Journal articles: 'Integrin modulation'

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Hughes, Paul E., and Martin Pfaff. "Integrin affinity modulation." Trends in Cell Biology 8, no. 9 (September 1998): 359–64. http://dx.doi.org/10.1016/s0962-8924(98)01339-7.

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Martin-Bermudo, Maria D., Olga M. Dunin-Borkowski, and Nicholas H. Brown. "Modulation of Integrin Activity is Vital for Morphogenesis." Journal of Cell Biology 141, no. 4 (May 18, 1998): 1073–81. http://dx.doi.org/10.1083/jcb.141.4.1073.

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Cells can vary their adhesive properties by modulating the affinity of integrin receptors. The activation and inactivation of integrins by inside-out mechanisms acting on the cytoplasmic domains of the integrin subunits has been demonstrated in platelets, lymphocytes, and keratinocytes. We show that in the embryo, normal morphogenesis requires the α subunit cytoplasmic domain to control integrin adhesion at the right times and places. PS2 integrin (αPS2βPS) adhesion is normally restricted to the muscle termini, where it is required for attaching the muscles to the ends of other muscles and to specialized epidermal cells. Replacing the wild-type αPS2 with mutant forms containing cytoplasmic domain deletions results in the rescue of the majority of defects associated with the absence of the αPS2 subunit, however, the mutant PS2 integrins are excessively active. Muscles containing these mutant integrins make extra muscle attachments at aberrant positions on the muscle surface, disrupting the muscle pattern and causing embryonic lethality. A gain- of-function phenotype is not observed in the visceral mesoderm, showing that regulation of integrin activity is tissue-specific. These results suggest that the αPS2 subunit cytoplasmic domain is required for inside-out regulation of integrin affinity, as has been seen with the integrin αIIbβ3.

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Tozer, Eileen Collins, Paul E. Hughes, and Joseph C. Loftus. "Ligand binding and affinity modulation of integrins." Biochemistry and Cell Biology 74, no. 6 (December 1, 1996): 785–98. http://dx.doi.org/10.1139/o96-085.

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Integrins are cell adhesion receptors that mediate cell–cell and cell–extracellular matrix interactions. The extracellular domains of these receptors possess binding sites for a diverse range of protein ligands. Ligand binding is divalent cation dependent and involves well-defined motifs in the ligand. Integrins can dynamically regulate their affinity for ligands (inside-out signaling). This ability to rapidly modulate their affinity state is key to their involvement in such processes as cell migration and platelet aggregation. This review will focus on two aspects of integrin function: first, on the molecular basis of ligand–integrin interactions and, second, on the underlying mechanisms controlling the affinity state of integrins for their ligands.Key words: integrins, ligand binding, affinity modulation.

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Ashe, Hilary L. "Modulation of BMP signalling by integrins." Biochemical Society Transactions 44, no. 5 (October 15, 2016): 1465–73. http://dx.doi.org/10.1042/bst20160111.

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The bone morphogenetic protein (BMP) pathway is a major conserved signalling pathway with diverse roles in development and homeostasis. Given that cells exist in three-dimensional environments, one important area is to understand how the BMP pathway operates within such complex cellular environments. The extracellular matrix contains information regarding tissue architecture and its mechanical properties that is transmitted to the cell via integrin receptors. In this review, I describe various examples of modulation of the BMP pathway by integrins. In the case of the Drosophila embryo and some cell line-based studies, integrins have been found to enhance BMP responses through different mechanisms, such as enhancement of BMP ligand–receptor binding and effects on Smad phosphorylation or stability. In these contexts, BMP-dependent activation of integrins is a common theme. However, I also discuss examples where integrins inhibit the BMP pathway, highlighting the context-dependent nature of integrin–BMP cross-talk.

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Huang, Jing, Lance C. Bridges, and Judith M. White. "Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family Members." Molecular Biology of the Cell 16, no. 10 (October 2005): 4982–91. http://dx.doi.org/10.1091/mbc.e05-03-0258.

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A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains.

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Mahabeleshwar, Ganapati H., Juhua Chen, Weiyi Feng, Payaningal R. Somanath, Olga V. Razorenova, and Tatiana V. Byzova. "Integrin affinity modulation in angiogenesis." Cell Cycle 7, no. 3 (February 2008): 335–47. http://dx.doi.org/10.4161/cc.7.3.5234.

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Woods, Anne, and John R. Couchman. "Integrin Modulation by Lateral Association." Journal of Biological Chemistry 275, no. 32 (May 4, 2000): 24233–36. http://dx.doi.org/10.1074/jbc.r000001200.

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Sethi, Tariq, Mark H. Ginsberg, Julian Downward, and Paul E. Hughes. "The Small GTP-binding Protein R-Ras Can Influence Integrin Activation by Antagonizing a Ras/Raf-initiated Integrin Suppression Pathway." Molecular Biology of the Cell 10, no. 6 (June 1999): 1799–809. http://dx.doi.org/10.1091/mbc.10.6.1799.

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The rapid modulation of ligand-binding affinity (“activation”) is a central property of the integrin family of cell adhesion receptors. The small GTP-binding protein Ras and its downstream effector kinase Raf-1 suppress integrin activation. In this study we explored the relationship between Ras and the closely related small GTP-binding protein R-Ras in modulating the integrin affinity state. We found that R-Ras does not seem to be a direct activator of integrins in Chinese hamster ovary cells. However, we observed that GTP-bound R-Ras strongly antagonizes the Ras/Raf-initiated integrin suppression pathway. Furthermore, this reversal of the Ras/Raf suppressor pathway does not seem to be via a competition between Ras and R-Ras for common downstream effectors or via an inhibition of Ras/Raf-induced MAP kinase activation. Thus, R-Ras and Ras may act in concert to regulate integrin affinity via the activation of distinct downstream effectors.

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Yu, Tao, Xing Wu, Kiran B. Gupta, and Dennis F. Kucik. "Affinity, lateral mobility, and clustering contribute independently to β2-integrin-mediated adhesion." American Journal of Physiology-Cell Physiology 299, no. 2 (August 2010): C399—C410. http://dx.doi.org/10.1152/ajpcell.00039.2009.

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Affinity changes and avidity modulation both contribute to activation of β2-integrin-mediated adhesion, an essential, early step in inflammation. Avidity modulation, defined as an increase in adhesiveness independent of integrin conformational changes, might be due to integrin clustering, motion, or both. Increased integrin diffusion upon leukocyte activation has been demonstrated, but whether it is proadhesive in itself, or just constitutes a mechanism for integrin clustering, remains unclear. To understand the proadhesive effects of integrin affinity changes, clustering, and motion, an experimental system was devised to separate them. Clustering and integrin motion together were induced by cytochalasin D (CD) without inducing high-affinity; integrin motion could then be frozen by fixation; and high affinity was induced independently by Mn2+. Adhesion was equivalent for fixed and unfixed cells except following pretreatment with CD or Mn2+, which increased adhesion for both. However, fixed cells were less adhesive than unfixed cells after CD, even though integrin clustering was similar. A simple explanation is that CD induces both clustering and integrin motion, fixation then stops motion on fixed cells, but integrins continue to diffuse on unfixed cells, increasing the kinetics of integrin/ICAM-1 interactions to enhance adhesion. Affinity changes are then independent of, and additive to, avidity effects.

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Anderson, M. J., Z. Q. Shi, and S. L. Zackson. "Proteolytic disruption of laminin-integrin complexes on muscle cells during synapse formation." Molecular and Cellular Biology 16, no. 9 (September 1996): 4972–84. http://dx.doi.org/10.1128/mcb.16.9.4972.

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To explore whether a neural modulation of muscle integrins' extracellular ligand interactions contributes to synapse induction, we compared the distributions of beta1-integrins and basal lamina proteins on Xenopus myotomal myocytes developing in culture. beta1-Integrins formed numerous organized aggregates scattered over the entire muscle surface, with particularly dense accumulations at specialized sites resembling myotendinous and neuromuscular junctions. Integrin aggregates on muscle cells differed from those on surrounding fibroblasts and epithelial cells, both in their lack of response to cross-linking by multivalent ligands and in their consistent association with the cells' own extracellular matrices. Muscle integrin clusters were usually associated with congruent basal lamina accumulations containing laminin and a heparan sulfate proteoglycan (HSPG), sometimes including fibronectin and vitronectin acquired from the surrounding medium. Immediately prior to synaptic differentiation, any existing laminin and HSPG accumulations along the path of cell contact were eliminated, disrupting otherwise stable laminin-integrin complexes. This apparently proteolytic modulation of integrins' extracellular ligand interactions was soon followed by the accumulation of new congruent accumulations of laminin and HSPG in the developing synaptic basal lamina. Combining these results with earlier findings, we consider the possibility that postsynaptic differentiation is induced, at least in part, by the proteolytic disruption of integrin-ligand complexes at sites of nerve-muscle contact.

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11

Berditchevski, Fedor. "Complexes of tetraspanins with integrins: more than meets the eye." Journal of Cell Science 114, no. 23 (December 1, 2001): 4143–51. http://dx.doi.org/10.1242/jcs.114.23.4143.

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The transmembrane proteins of the tetraspanin superfamily are implicated in a diverse range of biological phenomena, including cell motility, metastasis, cell proliferation and differentiation. The tetraspanins are associated with adhesion receptors of the integrin family and regulate integrin-dependent cell migration. In cells attached to the extracellular matrix, the integrin-tetraspanin adhesion complexes are clustered into a distinct type of adhesion structure at the cell periphery. Various tetraspanins are associated with phosphatidylinositol 4-kinase and protein kinase C isoforms, and they may facilitate assembly of signalling complexes by tethering these enzymes to integrin heterodimers. At the plasma membrane, integrin-tetraspanin signalling complexes are partitioned into specific microdomains proximal to cholesterol-rich lipid rafts. A substantial fraction of tetraspanins colocalise with integrins in various intracellular vesicular compartments. It is proposed that tetraspanins can influence cell migration by one of the following mechanisms: (1) modulation of integrin signalling; (2) compartmentalisation of integrins on the cell surface; or (3) direction of intracellular trafficking and recycling of integrins.

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12

Leisner, Tina M., June D. Wencel-Drake, Wei Wang, and Stephen C. T. Lam. "Bidirectional Transmembrane Modulation of Integrin αIIbβ3Conformations." Journal of Biological Chemistry 274, no. 18 (April 30, 1999): 12945–49. http://dx.doi.org/10.1074/jbc.274.18.12945.

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13

Kon, Shigeyuki, Hitomi Kouro, and Tadashi Matsuda. "A novel murine α4 integrin splicing variant is a specific receptor for VCAM-1 (61.2)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 61.2. http://dx.doi.org/10.4049/jimmunol.188.supp.61.2.

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Abstract Integrins affect multiple cell motility in control of cell survival, growth, or differentiation mediated by cell-cell and cell-extracellular matrix interaction. We previously reported that α9 integrin splicing variant, SFα9, promotes wild type α9 integrin-dependent adhesion. In this report, we introduce a new murine α4 integrin splicing variant mSFα4, which have new short cytoplasmic tail. In inflamed tissues including rheumatoid joint, the expression of mSFa4, as well as wild type α4 integrin, is upregulated. Interestingly, cells expressing mSFα4 bind to VCAM-1 but not other α4 integrin ligand such as fibronectin CS1 or osteopontin. Binding of cells coexpressing mSFα4 and wild type α4 integrin to α4 integrin ligands is promoted than cells expressing wild type α4 integrin. Thus, mSFα4 functions modulation of α4 integrin. Now, we pursue the metastatic function of mSFα4 by using mSFα4-specific knockdown tumor cells.

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Wu, Xin, Jon E. Mogford, Steven H. Platts, George E. Davis, Gerald A. Meininger, and Michael J. Davis. "Modulation of Calcium Current in Arteriolar Smooth Muscle by αvβ3 and α5β1 Integrin Ligands." Journal of Cell Biology 143, no. 1 (October 5, 1998): 241–52. http://dx.doi.org/10.1083/jcb.143.1.241.

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Vasoactive effects of soluble matrix proteins and integrin-binding peptides on arterioles are mediated by αvβ3 and α5β1 integrins. To examine the underlying mechanisms, we measured L-type Ca2+ channel current in arteriolar smooth muscle cells in response to integrin ligands. Whole-cell, inward Ba2+ currents were inhibited after application of soluble cyclic RGD peptide, vitronectin (VN), fibronectin (FN), either of two anti–β3 integrin antibodies, or monovalent β3 antibody. With VN or β3 antibody coated onto microbeads and presented as an insoluble ligand, current was also inhibited. In contrast, beads coated with FN or α5 antibody produced significant enhancement of current after bead attachment. Soluble α5 antibody had no effect on current but blocked the increase in current evoked by FN-coated beads and enhanced current when applied in combination with an appropriate IgG. The data suggest that αvβ3 and α5β1 integrins are differentially linked through intracellular signaling pathways to the L-type Ca2+ channel and thereby alter control of Ca2+ influx in vascular smooth muscle. This would account for the vasoactive effects of integrin ligands on arterioles and provide a potential mechanism for wound recognition during tissue injury.

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Mana, Giulia, Donatella Valdembri, Janet A. Askari, Zhenhai Li, Patrick Caswell, Cheng Zhu, Martin J. Humphries, Christoph Ballestrem, and Guido Serini. "The βI domain promotes active β1 integrin clustering into mature adhesion sites." Life Science Alliance 6, no. 2 (November 21, 2022): e202201388. http://dx.doi.org/10.26508/lsa.202201388.

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Modulation of integrin function is required in many physiological and pathological settings, such as angiogenesis and cancer. Integrin allosteric changes, clustering, and trafficking cooperate to regulate cell adhesion and motility on extracellular matrix proteins via mechanisms that are partly defined. By exploiting four monoclonal antibodies recognizing distinct conformational epitopes, we show that in endothelial cells (ECs), the extracellular βI domain, but not the hybrid or I-EGF2 domain of active β1 integrins, promotes their FAK-regulated clustering into tensin 1–containing fibrillar adhesions and impairs their endocytosis. In this regard, the βI domain–dependent clustering of active β1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by β1 integrin conformational activation alone.

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Vehlow, Anne, and Nils Cordes. "Growth factor receptor and β1 integrin signaling differentially regulate basal clonogenicity and radiation survival of fibroblasts via a modulation of cell cycling." In Vitro Cellular & Developmental Biology - Animal 58, no. 2 (February 2022): 169–78. http://dx.doi.org/10.1007/s11626-022-00656-z.

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AbstractCell adhesion to extracellular matrix proteins mediates resistance to radio- and chemotherapy by activating integrin signaling. In addition, mutual and cooperative interactions between integrin and growth factor receptor signaling contribute to the cellular radiation response. Here, we investigate to which extend the crosstalk between β1 integrins and growth factor receptor signaling determines the cellular radiation response of fibroblasts by assessing clonogenic survival and cell cycling. By utilizing growth factor signaling competent and either β1 integrin wildtype GD25β1A fibroblasts or β1 integrin mutant, signaling incompetent GD25β1B fibroblasts, we show basal clonogenic survival to depend on growth factor receptor but not integrin signaling. Our data further suggest the cooperation between β1 integrins and growth factor receptors to be critical for enhancing the radiation-induced G2/M cell cycle block leading to improved clonogenic radiation survival. By pharmacological inhibition of EGFR and PI3K, we additionally show that the essential contribution of EGFR signaling to radiogenic G2/M cell cycle arrest depends on the co-activation of the β1 integrin signaling axis, but occurs independent of PI3K. Taken together, elucidation of the signaling circuitry underlying the EGFR/β1 integrin crosstalk may support the development of advanced molecular targeted therapies for radiation oncology.

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Kinashi, Tatsuo, Tetsuo Asaoka, Ruri Setoguchi, and Kiyoshi Takatsu. "Affinity Modulation of Very Late Antigen-5 Through Phosphatidylinositol 3-Kinase in Mast Cells." Journal of Immunology 162, no. 5 (March 1, 1999): 2850–57. http://dx.doi.org/10.4049/jimmunol.162.5.2850.

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Abstract Adhesiveness of integrins is up-regulated rapidly by a number of molecules, including growth factors, cytokines, chemokines, and other cell surface receptors, through a mechanism termed inside-out signaling. The inside-out signaling pathways are thought to alter integrin affinity for ligand, or cell surface distribution of integrin by diffusion/clustering. However, it remains to be clarified whether any physiologically relevant agonists induce a rapid change in the affinity of β1 integrins and how ligand-binding affinity is modulated upon stimulation. In this study, we reported that affinity of β1 integrin very late Ag-5 (VLA-5) for fibronectin was rapidly increased in bone marrow-derived mast cells by Ag cross-linking of FcεRI. Ligand-binding affinity of VLA-5 was also augmented by receptor tyrosine kinases when the phospholipase Cγ-1/protein kinase C pathway was inhibited. Wortmannin suppressed induction of the high affinity state VLA-5 in either case. Conversely, introduction of a constitutively active p110 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) increased the binding affinity for fibronectin. Failure of a constitutively active Akt to stimulate adhesion suggested that the affinity modulation mechanisms mediated by PI 3-kinase are distinct from the mechanisms to control growth and apoptosis by PI 3-kinase. Taken together, our findings demonstrated that the increase of affinity of VLA-5 was induced by physiologically relevant stimuli and PI 3-kinase was a critical affinity modulator of VLA-5.

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Mousa, Shaker, Faith Davis, and Paul Davis. "Hormone-Integrin Cross Talk and Angiogenesis Modulation." Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry 9, no. 2 (June 1, 2009): 75–83. http://dx.doi.org/10.2174/187152209789000704.

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Grinnell, F. "Wound repair, keratinocyte activation and integrin modulation." Journal of Cell Science 101, no. 1 (January 1, 1992): 1–5. http://dx.doi.org/10.1242/jcs.101.1.1.

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Rico, Félix, Calvin Chu, Midhat H. Abdulreda, Yujing Qin, and Vincent T. Moy. "Temperature Modulation of Integrin-Mediated Cell Adhesion." Biophysical Journal 99, no. 5 (September 2010): 1387–96. http://dx.doi.org/10.1016/j.bpj.2010.06.037.

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Wei, Xiaofan, Xiang Wang, Jun Zhan, Yuhan Chen, Weigang Fang, Lingqiang Zhang, and Hongquan Zhang. "Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and degradation." Journal of Cell Biology 216, no. 5 (April 13, 2017): 1455–71. http://dx.doi.org/10.1083/jcb.201609073.

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Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates degradation of Kindlin-2 but not Talin, leading to inhibition of αIIbβ3 integrin activation in Chinese hamster ovary cells and β1 integrin activation in fibroblasts. Enhanced activation of β1 integrin was found in Smurf1-knockout mouse embryonic fibroblasts, which correlates with an increase in Kindlin-2 protein levels. Similarly, a reciprocal relationship between Smurf1 and Kindlin-2 protein levels is found in tissues from colon cancer patients, suggesting that Smurf1 mediates Kindlin-2 degradation in vivo. Collectively, we demonstrate that Smurf1 acts as a brake for integrin activation by controlling Kindlin-2 protein levels, a new mechanism that permits precise modulation of integrin-mediated cellular functions.

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Huttenlocher, A., M. H. Ginsberg, and A. F. Horwitz. "Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity." Journal of Cell Biology 134, no. 6 (September 15, 1996): 1551–62. http://dx.doi.org/10.1083/jcb.134.6.1551.

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Integrin cell surface adhesion receptors play a central role in mediating cell migration. We have developed a model system consisting of CHO cells ectopically expressing the alpha IIb beta 3 integrin to study integrin affinity and cytoskeletal interactions during cell migration. The alpha IIb beta 3 integrins are suited for study of integrin receptors during cell migration because they are well characterized with respect to ligand binding, cytoskeletal interactions, and signal transduction, and mutants with altered receptor function are available. The alpha IIb beta 3 receptor specifically mediates migration of alpha IIb beta 3-transfected CHO cells. The migration of transfected CHO cells was studied on a fibrinogen substrate both by time lapse videomicroscopy and by random and haptotactic transwell assays. Haptotactic and random transwell assays measured distinct aspects of migration, with the random transwell assay correlating most closely with time lapse videomicroscopy. Mutations in the cytoplasmic domains that increase ligand affinity or activation of the alpha IIb beta 3 receptor into a high affinity state by the LIBS6 antibody decreased the migration rate. Likewise, mutations that increase cytoskeletal organization without affecting affinity also decreased the migration rate. In contrast, truncation of the beta chain, which alters cytoskeletal associations as assayed by absence of focal adhesions, decreased haptotactic migration while increasing random migration. These effects on the migration rate were partially compensated for by altering substrate concentration, demonstrating optimum substrate concentrations that supported maximal migration. For example, cells expressing integrins locked in the high affinity state showed maximal migration at lower substrate concentrations than cells expressing low affinity receptor. Together, these results implicate the strength of adhesion between cell and substrate, as modulated by receptor affinity, organization of adhesive complexes, and substrate concentration, as important regulators of cell migration rate. Further, we demonstrate a dominant effect of high affinity integrin in inhibiting migration regardless of the organization of adhesive complexes. These observations have potential implications for tumor metastasis and its therapy.

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Thibault, Gaétan, Marie-Josée Lacombe, Lynn M. Schnapp, Alexandre Lacasse, Fatiha Bouzeghrane, and Geneviève Lapalme. "Upregulation of α8β1-integrin in cardiac fibroblast by angiotensin II and transforming growth factor-β1." American Journal of Physiology-Cell Physiology 281, no. 5 (November 1, 2001): C1457—C1467. http://dx.doi.org/10.1152/ajpcell.2001.281.5.c1457.

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Using a novel pharmacological tool with125I-echistatin to detect integrins on the cell, we have observed that cardiac fibroblasts harbor five different RGD-binding integrins: α8β1, α3β1, α5β1, αvβ1, and αvβ3. Stimulation of cardiac fibroblasts by angiotensin II (ANG II) or transforming growth factor-β1 (TGF-β1) resulted in an increase of protein and heightening by 50% of the receptor density of α8β1-integrin. The effect of ANG II was blocked by an AT1, but not an AT2, receptor antagonist, or by an anti-TGF-β1 antibody. ANG II and TGF-β1 increased fibronectin secretion, smooth muscle α-actin synthesis, and formation of actin stress fibers and enhanced attachment of fibroblasts to a fibronectin matrix. The α8- and β1-subunits were colocalized by immunocytochemistry with vinculin or β3-integrin at focal adhesion sites. These results indicate that α8β1-integrin is an abundant integrin on rat cardiac fibroblasts. Its positive modulation by ANG II and TGF-β1 in a myofibroblast-like phenotype suggests the involvement of α8β1-integrin in extracellular matrix protein deposition and cardiac fibroblast adhesion.

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Medhora, Meetha M. "Retinoic acid upregulates β1-integrin in vascular smooth muscle cells and alters adhesion to fibronectin." American Journal of Physiology-Heart and Circulatory Physiology 279, no. 1 (July 1, 2000): H382—H387. http://dx.doi.org/10.1152/ajpheart.2000.279.1.h382.

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Retinoic acid has an established physiological role in differentiation, development, and cellular growth. This study investigated the action of all- trans retinoic acid (ATRA) on vascular integrins, cell-surface receptors that control growth and remodeling of blood vessels. The β1-integrin subunit mRNA and protein was induced after treatment with ATRA in two different rat vascular smooth muscle cell lines. To relate this result to the in vivo state, the aortas from adult rats fed with therapeutic doses of ATRA were examined for β1-integrin protein. A significant upregulation of the integrin subunit was observed in vivo. To assess if this increase contributed to physiological changes in cellular function, cells treated with ATRA were tested for alterations in adhesion to extracellular matrix proteins. The cells exposed to the retinoid were seen to adhere more strongly to fibronectin, via the β1-integrin. These results showed that modulation of vascular integrins by ATRA in adult rats contributes to functional changes that can cause remodeling of blood vessels.

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Garcı́a, Andrés J., Marı́a D. Vega, and David Boettiger. "Modulation of Cell Proliferation and Differentiation through Substrate-dependent Changes in Fibronectin Conformation." Molecular Biology of the Cell 10, no. 3 (March 1999): 785–98. http://dx.doi.org/10.1091/mbc.10.3.785.

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Integrin-mediated cell adhesion to extracellular matrices provides signals essential for cell cycle progression and differentiation. We demonstrate that substrate-dependent changes in the conformation of adsorbed fibronectin (Fn) modulated integrin binding and controlled switching between proliferation and differentiation. Adsorption of Fn onto bacterial polystyrene (B), tissue culture polystyrene (T), and collagen (C) resulted in differences in Fn conformation as indicated by antibody binding. Using a biochemical method to quantify bound integrins in cultured cells, we found that differences in Fn conformation altered the quantity of bound α5 and β1integrin subunits but not αv or β3. C2C12 myoblasts grown on these Fn-coated substrates proliferated to different levels (B > T > C). Immunostaining for muscle-specific myosin revealed minimal differentiation on B, significant levels on T, and extensive differentiation on C. Differentiation required binding to the RGD cell binding site in Fn and was blocked by antibodies specific for this site. Switching between proliferation and differentiation was controlled by the levels of α5β1 integrin bound to Fn, and differentiation was inhibited by anti-α5, but not anti-αv, antibodies, suggesting distinct integrin-mediated signaling pathways. Control of cell proliferation and differentiation through conformational changes in extracellular matrix proteins represents a versatile mechanism to elicit specific cellular responses for biological and biotechnological applications.

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Belkin, Alexey M., S. Francesco Retta, Olga Y. Pletjushkina, Fiorella Balzac, Lorenzo Silengo, Reinhard Fassler, Victor E. Koteliansky, Keith Burridge, and Guido Tarone. "Muscle β1D Integrin Reinforces the Cytoskeleton–Matrix Link: Modulation of Integrin Adhesive Function by Alternative Splicing." Journal of Cell Biology 139, no. 6 (December 15, 1997): 1583–95. http://dx.doi.org/10.1083/jcb.139.6.1583.

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Expression of muscle-specific β1D integrin with an alternatively spliced cytoplasmic domain in CHO and GD25, β1 integrin-minus cells leads to their phenotypic conversion. β1D-transfected nonmuscle cells display rounded morphology, lack of pseudopodial activity, retarded spreading, reduced migration, and significantly enhanced contractility compared with their β1A-expressing counterparts. The transfected β1D is targeted to focal adhesions and efficiently displaces the endogenous β1A and αvβ3 integrins from the sites of cell–matrix contact. This displacement is observed on several types of extracellular matrix substrata and leads to elevated stability of focal adhesions in β1D transfectants. Whereas a significant part of cellular β1A integrin is extractable in digitonin, the majority of the transfected β1D is digitonin-insoluble and is strongly associated with the detergent-insoluble cytoskeleton. Increased interaction of β1D integrin with the actin cytoskeleton is consistent with and might be mediated by its enhanced binding to talin. In contrast, β1A interacts more strongly with α-actinin, than β1D. Inside-out driven activation of the β1D ectodomain increases ligand binding and fibronectin matrix assembly by β1D transfectants. Phenotypic effects of β1D integrin expression in nonmuscle cells are due to its enhanced interactions with both cytoskeletal and extracellular ligands. They parallel the transitions that muscle cells undergo during differentiation. Modulation of β1 integrin adhesive function by alternative splicing serves as a physiological mechanism reinforcing the cytoskeleton– matrix link in muscle cells. This reflects the major role for β1D integrin in muscle, where extremely stable association is required for contraction.

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Bloch, Wilhelm, Yun Fan, Ji Han, Sheng Xue, Torsten Schöneberg, Guanju Ji, Zhong J. Lu, et al. "Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins." Journal of Cell Biology 154, no. 4 (August 20, 2001): 753–62. http://dx.doi.org/10.1083/jcb.200103011.

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β1 integrins play a crucial role as cytoskeletal anchorage proteins. In this study, the coupling of the cytoskeleton and intracellular signaling pathways was investigated in β1 integrin deficient (−/−) embryonic stem cells. Muscarinic inhibition of the L-type Ca2+ current (ICa) and activation of the acetylcholine-activated K+ current (IK,ACh) was found to be absent in β1 integrin−/− cardiomyocytes. Conversely, β adrenoceptor-mediated modulation of ICa was unaffected by the absence of β1 integrins. This defect in muscarinic signaling was due to defective G protein coupling. This was supported by deconvolution microscopy, which demonstrated that Gi exhibited an atypical subcellular distribution in the β1 integrin−/− cardiomyocytes. A critical role of the cytoskeleton was further demonstrated using cytochalasin D, which displaced Gi and impaired muscarinic signaling. We conclude that cytoskeletal integrity is required for correct localization and function of Gi-associated signaling microdomains.

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Babbitt, Christopher J., Shaw-Yung Shai, Alice E. Harpf, Can G. Pham, and Robert S. Ross. "Modulation of integrins and integrin signaling molecules in the pressure-loaded murine ventricle." Histochemistry and Cell Biology 118, no. 6 (December 2002): 431–39. http://dx.doi.org/10.1007/s00418-002-0476-1.

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Kertsman, J., E. Cohen, M. Abdellatif, and R. Wieder. "Modulation of integrin α5 in head and neck cancer cells by epidermal growth factor and its contribution to the malignant phenotype." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 15512. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.15512.

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15512 Background: The primary therapy for head and neck cancer consists of combination treatment with radiation and chemotherapy. While this combined modality approach is often curative, a significant fraction of patients have residual viable tumor cells after treatment that can result in progressive disease or relapse. We hypothesize that a significant contribution of cell survival results from interaction of cancer cells with the tumor microenvironment that includes soluble ligands of growth factor receptors and structural ligands of cell surface adhesion molecules. One of the growth factors with reported tumor survival effects is epidermal growth factor (EGF). We investigated the contribution of EGF to the relationship of 1483 head and neck cancer cells with their microenvironment. Methods: We treated 1483 head and neck cancer cells with variable concentrations of EGF from 0.1 to 20 nM and carried out western blots and flow cytometry to determine the expression of relevant integrins. Effects of interventions were evaluated by soft agar colony assays, proliferation and survival in tissue culture and adhesion to culture plates coated with integrin ligands. Results: Western blots demonstrated an EGF-induced increase in the expression of intgerin α5 but no change in the expression of integrins α2 or β1. The presence of dissolved fibronectin, a ligand of integrin α5β1, but not of collagen I, a ligand of integrin α2β1, provided a survival advantage to colonies in soft agar in EGF-treated cells. Experiments are determining whether this survival advantage translates to a shift in the dose-response curve to paclitaxel and ionizing radiation, on activation of caspases 3 and 8 and cleavage of poly (ADP- ribose) polymerase (PARP). These data are being correlated with EGF-induced modulation of adhesion to fibronectin, collagen and control plates. We have constructed adenoviral vectors expressing short hairpin RNA (shRNA) sequences to integrins α5 and α2 to confirm the role of integrin α5 expression in the EGF-induced modulation of survival. Conclusions: These data support a potential contribution to survival of head and neck cancer cells by modulation of integrins by EGF through interaction with their ligands in the microenvironment. No significant financial relationships to disclose.

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Cattelino, Anna, Chiara Albertinazzi, Mario Bossi, David R. Critchley, and Ivan de Curtis. "A Cell-free System to Study Regulation of Focal Adhesions and of the Connected Actin Cytoskeleton." Molecular Biology of the Cell 10, no. 2 (February 1999): 373–91. http://dx.doi.org/10.1091/mbc.10.2.373.

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Assembly and modulation of focal adhesions during dynamic adhesive processes are poorly understood. We describe here the use of ventral plasma membranes from adherent fibroblasts to explore mechanisms regulating integrin distribution and function in a system that preserves the integration of these receptors into the plasma membrane. We find that partial disruption of the cellular organization responsible for the maintenance of organized adhesive sites allows modulation of integrin distribution by divalent cations. High Ca2+ concentrations induce quasi-reversible diffusion of β1 integrins out of focal adhesions, whereas low Ca2+ concentrations induce irreversible recruitment of β1 receptors along extracellular matrix fibrils, as shown by immunofluorescence and electron microscopy. Both effects are independent from the presence of actin stress fibers in this system. Experiments with cells expressing truncated β1 receptors show that the cytoplasmic portion of β1 is required for low Ca2+-induced recruitment of the receptors to matrix fibrils. Analysis with function-modulating antibodies indicates that divalent cation-mediated receptor distribution within the membrane correlates with changes in the functional state of the receptors. Moreover, reconstitution experiments show that purified α-actinin colocalizes and redistributes with β1 receptors on ventral plasma membranes depleted of actin, implicating binding of α-actinin to the receptors. Finally, we found that recruitment of exogenous actin is specifically restricted to focal adhesions under conditions in which new actin polymerization is inhibited. Our data show that the described system can be exploited to investigate the mechanisms of integrin function in an experimental setup that permits receptor redistribution. The possibility to uncouple, under cell-free conditions, events involved in focal adhesion and actin cytoskeleton assembly should facilitate the comprehension of the underlying molecular mechanisms.

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Shattil, S. J., T. O'Toole, M. Eigenthaler, V. Thon, M. Williams, B. M. Babior, and M. H. Ginsberg. "Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit." Journal of Cell Biology 131, no. 3 (November 1, 1995): 807–16. http://dx.doi.org/10.1083/jcb.131.3.807.

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The adhesive and signaling functions of integrins are regulated through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated beta 3-endonexin, that interacted with the cytoplasmic tail of the beta 3 integrin subunit in a yeast two-hybrid system. This interaction is structurally specific, since it was reduced by 64% by a point mutation in the beta 3 cytoplasmic tail (S752-->P) that disrupts integrin signaling. Moreover, this interaction is integrin subunit specific since it was not observed with the cytoplasmic tails of the alpha IIb, beta 1, or beta 2 subunits. beta 3-Endonexin fusion proteins bound selectively to detergent-solubilized beta 3 from platelets and human umbilical vein endothelial cells, and beta 3-endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to beta integrin tails. The apparent specificity of beta 3-endonexin for the beta 3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions.

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Goel, Hira Lal, Mara Fornaro, Loredana Moro, Natalia Teider, Johng S. Rhim, Michael King, and Lucia R. Languino. "Selective modulation of type 1 insulin-like growth factor receptor signaling and functions by β1 integrins." Journal of Cell Biology 166, no. 3 (August 2, 2004): 407–18. http://dx.doi.org/10.1083/jcb.200403003.

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We show here that β1 integrins selectively modulate insulin-like growth factor type I receptor (IGF-IR) signaling in response to IGF stimulation. The β1A integrin forms a complex with the IGF-IR and insulin receptor substrate-1 (IRS-1); this complex does not promote IGF-I mediated cell adhesion to laminin (LN), although it does support IGF-mediated cell proliferation. In contrast, β1C, an integrin cytoplasmic variant, increases cell adhesion to LN in response to IGF-I and its down-regulation by a ribozyme prevents IGF-mediated adhesion to LN. Moreover, β1C completely prevents IGF-mediated cell proliferation and tumor growth by inhibiting IGF-IR auto-phosphorylation in response to IGF-I stimulation. Evidence is provided that the β1 cytodomain plays an important role in mediating β1 integrin association with either IRS-1 or Grb2-associated binder1 (Gab1)/SH2-containing protein-tyrosine phosphate 2 (Shp2), downstream effectors of IGF-IR: specifically, β1A associates with IRS-1 and β1C with Gab1/Shp2. This study unravels a novel mechanism mediated by the integrin cytoplasmic domain that differentially regulates cell adhesion to LN and cell proliferation in response to IGF.

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Kimmins, Sarah, and Leslie A. MacLaren. "Cyclic Modulation of Integrin Expression in Bovine Endometrium1." Biology of Reproduction 61, no. 5 (November 1, 1999): 1267–74. http://dx.doi.org/10.1095/biolreprod61.5.1267.

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DICKESON, S., T. STRICKER, A. BENTON, Y. PAN, and S. SANTORO. "Affinity modulation of the α2 integrin I domain." Matrix Biology 25 (November 2006): S52. http://dx.doi.org/10.1016/j.matbio.2006.08.144.

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Zaveri, Toral D., Jamal S. Lewis, Natalia V. Dolgova, Michael J. Clare-Salzler, and Benjamin G. Keselowsky. "Integrin-directed modulation of macrophage responses to biomaterials." Biomaterials 35, no. 11 (April 2014): 3504–15. http://dx.doi.org/10.1016/j.biomaterials.2014.01.007.

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Ducharme, Lori A., and John H. Weis. "Modulation of integrin expression during mast cell differentiation." European Journal of Immunology 22, no. 10 (October 1992): 2603–7. http://dx.doi.org/10.1002/eji.1830221020.

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Bosquetti, Bruna, Aline Aparecida Santana, Paulo Cézar Gregório, Regiane Stafim da Cunha, Guilherme Miniskiskosky, Julia Budag, Célia Regina Cavichiolo Franco, Edneia Amancio de Souza Ramos, Fellype Carvalho Barreto, and Andréa Emilia Marques Stinghen. "The Role of α3β1 Integrin Modulation on Fabry Disease Podocyte Injury and Kidney Impairment." Toxins 15, no. 12 (December 14, 2023): 700. http://dx.doi.org/10.3390/toxins15120700.

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Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3β1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances in these integrins can lead to podocyte injury. Therefore, this study aimed to assess the effects of chloroquine (CQ) on podocytes, as this drug can be used to obtain an in vitro condition analogous to the FD. Murine podocytes were employed in our experiments. The results revealed a dose-dependent reduction in cell viability. CQ at a sub-lethal concentration (1.0 µg/mL) induced lysosomal accumulation significantly (p < 0.0001). Morphological changes were evident through scanning electron microscopy and immunofluorescence, highlighting alterations in F-actin and nucleus morphology. No significant changes were observed in the gene expression of α3β1 integrins via RT-qPCR. Protein expression of α3 integrin was evaluated with Western Blotting and immunofluorescence, demonstrating its lower detection in podocytes exposed to CQ. Our findings propose a novel in vitro model for exploring secondary Fabry nephropathy, indicating a modulation of α3β1 integrin and morphological alterations in podocytes under the influence of CQ.

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Gout, Stéphanie P., Muriel R. Jacquier-Sarlin, Laurence Rouard-Talbot, Patricia Rousselle, and Marc R. Block. "RhoA-dependent Switch between α2β1 and α3β1 Integrins Is Induced by Laminin-5 during Early Stage of HT-29 Cell Differentiation." Molecular Biology of the Cell 12, no. 10 (October 2001): 3268–81. http://dx.doi.org/10.1091/mbc.12.10.3268.

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Integrin-mediated interactions between the basement membrane and epithelial cells control the differentiation of epithelia. We characterized the modulation of adhesive behaviors to basement membrane proteins and of integrin function in the human colon adenocarcinoma HT-29 cell line, which differentiates into enterocytes after the substitution of galactose for glucose in the medium. We demonstrate an increased capability of these cells to adhere to collagen type IV during the early stage of differentiation. This effect occurs without any changes in integrin cell surface expression but rather results from an α2β1/α3β1 integrin switch, α3β1 integrin becoming the major collagen receptor. The increase in laminin-5 secretion and deposit on the matrix is a key factor in the mechanism regulating cell adhesion, because it is responsible for the activation of α3β1 integrin. Furthermore, down-regulation of RhoA GTPase activity occurs during HT-29 cell differentiation and correlates with the activation of the integrin α3β1. Indeed, C3 transferase, a RhoA GTPase inhibitor, induces a similar α2β1/α3β1 switch in undifferentiated HT-29 cells. These results indicate that the decrease in RhoA activation is the biochemical mechanism underlying this integrin switch observed during cell differentiation. The physiological relevance of such modulation of integrin activity in the functioning of the crypt-villus axis is discussed.

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Mana, Giulia, Donatella Valdembri, and Guido Serini. "Conformationally active integrin endocytosis and traffic: why, where, when and how?" Biochemical Society Transactions 48, no. 1 (February 17, 2020): 83–93. http://dx.doi.org/10.1042/bst20190309.

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Spatiotemporal control of integrin-mediated cell adhesion to the extracellular matrix (ECM) is critical for physiological and pathological events in multicellular organisms, such as embryonic development, angiogenesis, platelet aggregation, leukocytes extravasation, and cancer cell metastatic dissemination. Regulation of integrin adhesive function and signaling relies on the modulation of both conformation and traffic. Indeed, integrins exist in a dynamic equilibrium between a bent/closed (inactive) and an extended/open (active) conformation, respectively endowed with low and high affinity for ECM ligands. Increasing evidence proves that, differently to what hypothesized in the past, detachment from the ECM and conformational inactivation are not mandatory for integrin to get endocytosed and trafficked. Specific transmembrane and cytosolic proteins involved in the control of ECM proteolytic fragment-bound active integrin internalization and recycling exist. In the complex masterplan that governs cell behavior, active integrin traffic is key to the turnover of ECM polymers and adhesion sites, the polarized secretion of endogenous ECM proteins and modifying enzymes, the propagation of motility and survival endosomal signals, and the control of cell metabolism.

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Shewchuk, Lee J., Sean Bryan, Marina Ulanova, and Neelam Khaper. "Integrin β3 prevents apoptosis of HL-1 cardiomyocytes under conditions of oxidative stressThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease." Canadian Journal of Physiology and Pharmacology 88, no. 3 (March 2010): 324–30. http://dx.doi.org/10.1139/y09-131.

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Integrin receptors are essential in the regulation of vital cardiac functions, and impaired integrin activity has been associated with cardiac remodeling. Oxidative stress is known to be involved in apoptosis and cardiac remodeling and thus may profoundly influence cardiac function via integrin modulation. The aim of this study was to determine the expression pattern and functional role of integrins in HL-1 cardiomyocytes under conditions of oxidative stress. Gene expression was studied by end-point and real-time PCR; surface protein expression was studied by flow cytometry; integrin knockdown was accomplished by siRNA gene silencing; and apoptosis was studied by annexin V staining and active caspase-3/7 using flow cytometry. Among the various subunits under study (αv, α5, α6, and β1, β3, β4, and β5), the expression of β3 integrin was significantly increased at both the mRNA and protein levels in cardiomyocytes exposed to 100 µmol/L hydrogen peroxide for 3 h. Gene silencing of β3 integrin by using siRNA resulted in a 2-fold increase in cardiomyocyte apoptosis upon treatment with hydrogen peroxide. This increase in apoptosis, as measured by annexin V staining, correlated with an increase in active caspase-3/7. Integrin β3 plays a vital role in preventing cardiomyocyte apoptosis under conditions of oxidative stress.

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AlJamal-Naylor, Rehab, Linda Wilson, Susan McIntyre, Fiona Rossi, Beth Harrison, Mark Marsden, and David J. Harrison. "Allosteric Modulation of Beta1 Integrin Function Induces Lung Tissue Repair." Advances in Pharmacological Sciences 2012 (2012): 1–16. http://dx.doi.org/10.1155/2012/768720.

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The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.

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Hato, Takaaki, Nisar Pampori, and Sanford J. Shattil. "Complementary Roles for Receptor Clustering and Conformational Change in the Adhesive and Signaling Functions of Integrin αIIbβ3." Journal of Cell Biology 141, no. 7 (June 29, 1998): 1685–95. http://dx.doi.org/10.1083/jcb.141.7.1685.

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Integrin αIIbβ3 mediates platelet aggregation and “outside-in” signaling. It is regulated by changes in receptor conformation and affinity and/or by lateral diffusion and receptor clustering. To document the relative contributions of conformation and clustering to αIIbβ3 function, αIIb was fused at its cytoplasmic tail to one or two FKBP12 repeats (FKBP). These modified αIIb subunits were expressed with β3 in CHO cells, and the heterodimers could be clustered into morphologically detectable oligomers upon addition of AP1510, a membrane-permeable, bivalent FKBP ligand. Integrin clustering by AP1510 caused binding of fibrinogen and a multivalent (but not monovalent) fibrinogen-mimetic antibody. However, ligand binding due to clustering was only 25–50% of that observed when αIIbβ3 affinity was increased by an activating antibody or an activating mutation. The effects of integrin clustering and affinity modulation were additive, and clustering promoted irreversible ligand binding. Clustering of αIIbβ3 also promoted cell adhesion to fibrinogen or von Willebrand factor, but not as effectively as affinity modulation. However, clustering was sufficient to trigger fibrinogen-independent tyrosine phosphorylation of pp72Syk and fibrinogen-dependent phosphorylation of pp125FAK, even in non-adherent cells. Thus, receptor clustering and affinity modulation play complementary roles in αIIbβ3 function. Affinity modulation is the predominant regulator of ligand binding and cell adhesion, but clustering increases these responses further and triggers protein tyrosine phosphorylation, even in the absence of affinity modulation. Both affinity modulation and clustering may be needed for optimal function of αIIbβ3 in platelets.

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Hangan-Steinman, Dolores, Wai-chi Ho, Priti Shenoy, Bosco MC Chan, and Vincent L. Morris. "Differences in phosphatase modulation of α4 β1 and α5 β1 integrin-mediated adhesion and migration of B16F1 cells." Biochemistry and Cell Biology 77, no. 5 (October 1, 1999): 409–20. http://dx.doi.org/10.1139/o99-050.

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It is well established that a biphasic relationship exists between the adhesive strength of β1 integrins and their ability to mediate cell movement. Thus, cell movement increases progressively with adhesive strength, but beyond a certain point of optimal interaction, cell movement is reduced with further increases in adhesive function. The interplay between the various kinase and phosphatase activities provides the balance in β1 integrin-mediated cell adhesion and migration. In the present study, the significance of protein tyrosine phosphatases (PTP) and ser/thr protein phosphatases (PP) in α4β1 and α5β1 integrin-mediated mouse melanoma B16F1 cell anchorage and migration on fibronectin was characterized using phosphatase inhibitors. At low fibronectin concentration, α5β1 functioned as the predominant receptor for cell movement; a role for α4β1 in B16F1 cell migration increased progressively with fibronectin concentration. Treatment of B16F1 cells with PTP inhibitors, sodium orthovanadate (Na3VO4) and phenylarsine oxide (PAO), or PP-1/2A inhibitor, okadaic acid (OA), abolished cell movement. Inhibition of cell movement by PAO and OA was associated by a reduction in the adhesive strength of α4β1 and α5β1. In contrast, treatment of B16F1 cells with Na3VO4 resulted in selective stimulation of the adhesive function of α5β1, but not α4β1. Therefore, our results demonstrate that (i) both PTP and PP-1/2A have roles in cell movement, (ii) modulation of cell movement by PTP and PP-1/2A may involve either a stimulation or reduction of β1 integrin adhesive strength, and (iii) distinct phosphatase-mediated signaling pathways for differential regulation of the various β1 integrins exist. Key words: phosphatases, integrins, cell movement, cell adhesion.

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Davis-Lunn, Mathew, Benjamin T. Goult, and Melissa R. Andrews. "Clutching at Guidance Cues: The Integrin–FAK Axis Steers Axon Outgrowth." Biology 12, no. 7 (July 3, 2023): 954. http://dx.doi.org/10.3390/biology12070954.

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Integrin receptors are essential contributors to neurite outgrowth and axon elongation. Activated integrins engage components of the extracellular matrix, enabling the growth cone to form point contacts, which connect the extracellular substrate to dynamic intracellular protein complexes. These adhesion complexes facilitate efficient growth cone migration and neurite extension. Major signalling pathways mediated by the adhesion complex are instigated by focal adhesion kinase (FAK), whilst axonal guidance molecules present in vivo promote growth cone turning or retraction by local modulation of FAK activity. Activation of FAK is marked by phosphorylation following integrin engagement, and this activity is tightly regulated during neurite outgrowth. FAK inhibition slows neurite outgrowth by reducing point contact turnover; however, mutant FAK constructs with enhanced activity stimulate aberrant outgrowth. Importantly, FAK is a major structural component of maturing adhesion sites, which provide the platform for actin polymerisation to drive leading edge advance. In this review, we discuss the coordinated signalling of integrin receptors and FAK, as well as their role in regulating neurite outgrowth and axon elongation. We also discuss the importance of the integrin–FAK axis in vivo, as integrin expression and activation are key determinants of successful axon regeneration following injury.

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Symington, B. E., and W. G. Carter. "Modulation of epidermal differentiation by epiligrin and integrin alpha 3 beta 1." Journal of Cell Science 108, no. 2 (February 1, 1995): 831–38. http://dx.doi.org/10.1242/jcs.108.2.831.

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We previously reported that integrin alpha 3 beta 1 mediates epidermal intercellular adhesion as well as cell-substrate adhesion. P1B5, an anti-alpha 3 beta 1 specific monoclonal antibody, is a potent in vitro trigger of epidermal cell-cell adhesion and an inhibitor of cell-substrate adhesion. We now show that P1B5 specifically induces the intercellular localization of integrins alpha 2 beta 1 and alpha 3 beta 1, consistent with its role in inducing intercellular adhesion via these two integrins. P1F2, another anti-alpha 3 beta 1 antibody, does not induce either intercellular adhesion or intercellular accumulation of alpha 3 beta 1 and alpha 2 beta 1. Growth of epidermal cells in high calcium, known to induce epidermal differentiation, also induces intercellular accumulation of alpha 3 beta 1 and alpha 2 beta 1 and increased cell-cell adhesion. We therefore asked whether P1B5 treatment induces epidermal differentiation. P1B5 treatment induces changes consistent with epidermal differentiation, including increased involucrin expression, stratification, and production of squames. P1F2 treatment has none of these effects. In vivo, epidermal basal cells are in close contact with the epithelial basement membrane component epiligrin. Growth of keratinocytes on purified epiligrin but not other matrix components specifically reduces involucrin expression by P1B5-treated keratinocytes. These results suggest that integrin alpha 3 beta 1 has a unique role in epidermal differentiation, that the epitope recognized by P1B5 is involved in triggering this differentiation, and that keratinocyte adhesion to epiligrin inhibits alpha 3 beta 1-mediated differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Pal, Sekhar, Kirat Kumar Ganguly, Shuvojit Moulik, and Amitava Chatterjee. "Modulation of MMPs by Cell Surface Integrin Receptor α5β1." Anti-Cancer Agents in Medicinal Chemistry 12, no. 7 (August 1, 2012): 726–32. http://dx.doi.org/10.2174/187152012802650183.

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Kinashi, Tatsuo, Ruri Wada, Masayo Inaba, Tetsuo Asaoka, and Kiyoshi Takatsu. "Mechanisms of avidity modulation of integrin in mast cells." Ensho 16, no. 3 (1996): 163–69. http://dx.doi.org/10.2492/jsir1981.16.163.

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Rose, David M., Ronen Alon, and Mark H. Ginsberg. "Integrin modulation and signaling in leukocyte adhesion and migration." Immunological Reviews 218, no. 1 (August 2007): 126–34. http://dx.doi.org/10.1111/j.1600-065x.2007.00536.x.

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Zheng, Duo-Qi, Mara Fornaro, Cindy J. M. Bofetiado, Giovanni Tallini, Silvano Bosari, and Lucia R. Languino. "Modulation of cell proliferation by the integrin cytoplasmic domain." Kidney International 51, no. 5 (May 1997): 1434–40. http://dx.doi.org/10.1038/ki.1997.196.

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Kim, Seon-Myung, Min Seong Kwon, Chun Shik Park, Kyeong-Rock Choi, Jang-Soo Chun, Joohong Ahn, and Woo Keun Song. "Modulation of Thr Phosphorylation of Integrin β1during Muscle Differentiation." Journal of Biological Chemistry 279, no. 8 (December 2, 2003): 7082–90. http://dx.doi.org/10.1074/jbc.m311581200.

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Journal articles on the topic 'Integrin modulation'

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