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This paper describes one of the possible mechanisms whereby αvβ3-mediated adhesion results in enhanced signalling from the insulin-like growth factor-1 (IGF-1) receptor. When αvβ3 is prevented from ligand occupancy by the disintegrin echistatin, the IGF-1 receptor directly recruits the tyrosine phosphatase Shp2, which in turn reduces the phosphorylation levels of the receptor.
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Maile L.A., Clemmons D.R. The αvβ3 integrin regulates insulin-like growth factor (IGF-I) receptor phosphorylation by altering the rate of recruitment of the Src-homology 2-containing phosphotyrosine phosphatase-2 to the activated IGF-I receptor. Endocrinology. 143: 2002;4259-4264 This paper describes one of the possible mechanisms whereby αvβ3-mediated adhesion results in enhanced signalling from the insulin-like growth factor-1 (IGF-1) receptor. When αvβ3 is prevented from ligand occupancy by the disintegrin echistatin, the IGF-1 receptor directly recruits the tyrosine phosphatase Shp2, which in turn reduces the phosphorylation levels of the receptor.
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•]) shows that interactions between integrins and growth factor receptors, together with integrin engagement by axonal ligands, drive the developmental stages of oligodendrocyte maturation. In oligodendrocyte progenitors, platelet-derived growth factor (PDGF)-dependent mitogenic activity requires association of the PDGF receptor with αvβ3 integrin, which leads to PDGF-induced, protein-kinase-C-dependent activation of αvβ3, mediated by an increase in the affinity for matrix ligands. In turn, integrin activation results in the stimulation of an adhesion-dependent phosphatidylinositol 3-kinase pathway that promotes oligodendrocyte proliferation. During the transition from progenitor cell to mature cell, oligodendrocytes require survival signals provided by the integration of short-range cues from the extracellular matrix with long-range growth factor signals.
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•]) shows that interactions between integrins and growth factor receptors, together with integrin engagement by axonal ligands, drive the developmental stages of oligodendrocyte maturation. In oligodendrocyte progenitors, platelet-derived growth factor (PDGF)-dependent mitogenic activity requires association of the PDGF receptor with αvβ3 integrin, which leads to PDGF-induced, protein-kinase-C-dependent activation of αvβ3, mediated by an increase in the affinity for matrix ligands. In turn, integrin activation results in the stimulation of an adhesion-dependent phosphatidylinositol 3-kinase pathway that promotes oligodendrocyte proliferation. During the transition from progenitor cell to mature cell, oligodendrocytes require survival signals provided by the integration of short-range cues from the extracellular matrix with long-range growth factor signals. Specifically, when oligodendrocytes locally contact axonal laminins through α6β1, they begin mounting a survival response following stimulation with diffusible neuregulin, PDGF, or subliminal concentration of both.
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An equanimous and highly informative review on the many, and often contradictory, aspects of α6β4-dependent signals and biological effects.
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Mercurio A.M., Rabinovitz I., Shaw L.M. The α6β4 integrin and epithelial cell migration. Curr Opin Cell Biol. 13:2001;541-545 An equanimous and highly informative review on the many, and often contradictory, aspects of α6β4-dependent signals and biological effects.
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This paper shows that an epidermal growth factor (EGF)-triggered signalling complex consisting of the EGF receptor, the cytosolic tyrosine kinase Fyn and the α6β4 integrin promotes hemidesmosome disassembly in epithelial cells and stimulates cell invasion. This is accomplished through EGF-receptor-dependent activation of Fyn, which in turn phosphorylates the β4 cytoplasmic domain. Expression of dominant-negative Fyn isoforms in carcinoma cells increases hemidesmosome formation, impairs EGF-dependent migration in vitro, and reduces lung metastases following intravenous injection in nude mice.
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VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells
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This paper shows for the first time that endothelial cells sense shear stress through a multimolecular complex consisting of vascular endothelial growth factor (VEGF) receptor-2, VE-cadherin and β-catenin. Shear stress stimulates induction and nuclear translocation of VEGF receptor-2, as well as its association with VE-cadherin and β-catenin at cell-cell adhesion sites. In endothelial cells lacking VE-cadherin, shear stress does not promote nuclear translocation of VEGF receptor and does not induce transcription of a reporter gene under the control of a shear-stress-responsive promoter.
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Shay-Salit A., Shushy M., Wolfovitz E., Yahav H., Breviario F., Dejana E., Resnick N. VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells. Proc Natl Acad Sci USA. 99:2002;9462-9467 This paper shows for the first time that endothelial cells sense shear stress through a multimolecular complex consisting of vascular endothelial growth factor (VEGF) receptor-2, VE-cadherin and β-catenin. Shear stress stimulates induction and nuclear translocation of VEGF receptor-2, as well as its association with VE-cadherin and β-catenin at cell-cell adhesion sites. In endothelial cells lacking VE-cadherin, shear stress does not promote nuclear translocation of VEGF receptor and does not induce transcription of a reporter gene under the control of a shear-stress-responsive promoter.
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(2002)
Proc Natl Acad Sci USA
, vol.99
, pp. 9462-9467
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Shay-Salit, A.1
Shushy, M.2
Wolfovitz, E.3
Yahav, H.4
Breviario, F.5
Dejana, E.6
Resnick, N.7
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43
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0034945537
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N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling
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This paper provides an insightful analysis of the signalling mechanisms underlying the pro-adhesive function of N-CAM in β cells from pancreatic tumours. N-CAM stimulates β1-integrin-dependent matrix adhesion by assembling a huge multimolecular complex comprising, among others, N-cadherin, fibroblast growth factor receptor (FGFR) 4, and phospholipase Cγ. Dominant-negative variants of FGFR-4, inhibitors of FGFR-4 signalling, and function-blocking antibodies against β1 integrins impair NCAM-induced adhesion.
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Cavallaro U., Niedermeyer J., Fuxa M., Christofori G. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Nat Cell Biol. 3:2001;650-657 This paper provides an insightful analysis of the signalling mechanisms underlying the pro-adhesive function of N-CAM in β cells from pancreatic tumours. N-CAM stimulates β1-integrin-dependent matrix adhesion by assembling a huge multimolecular complex comprising, among others, N-cadherin, fibroblast growth factor receptor (FGFR) 4, and phospholipase Cγ. Dominant-negative variants of FGFR-4, inhibitors of FGFR-4 signalling, and function-blocking antibodies against β1 integrins impair NCAM-induced adhesion.
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(2001)
Nat Cell Biol
, vol.3
, pp. 650-657
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Cavallaro, U.1
Niedermeyer, J.2
Fuxa, M.3
Christofori, G.4
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44
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0034731148
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Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation
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Pece S., Gutkind J.S. Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation. J Biol Chem. 275:2000;41227-41233.
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(2000)
J Biol Chem
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, pp. 41227-41233
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Pece, S.1
Gutkind, J.S.2
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45
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0037020084
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Rac activation upon cell-cell contact formation is dependent on signaling from the epidermal growth factor receptor
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These papers (see also Pece and Gutkind [2000] [44]) provide two examples of intracellular signals triggered by intercellular adhesion as a consequence of ligand-independent activation of the epidermal growth factor (EGF) receptor. Formation of cell-cell contacts between neighbouring cells leads to association of E-cadherin to the EGF receptor, receptor transactivation, Shc phosphorylation and stimulation of mitogen-activated protein kinase (MAPK) activity. Moreover, induction of intercellular adhesion results in Rac activation, which can be blocked by pharmacological inhibitors of the EGF receptor, but not by inhibitors of phosphatidylinositol 3-kinase or MAPK.
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Betson M., Lozano E., Zhang J., Braga V.M. Rac activation upon cell-cell contact formation is dependent on signaling from the epidermal growth factor receptor. J Biol Chem. 277:2002;36962-36969 These papers (see also Pece and Gutkind [2000] [44]) provide two examples of intracellular signals triggered by intercellular adhesion as a consequence of ligand-independent activation of the epidermal growth factor (EGF) receptor. Formation of cell-cell contacts between neighbouring cells leads to association of E-cadherin to the EGF receptor, receptor transactivation, Shc phosphorylation and stimulation of mitogen-activated protein kinase (MAPK) activity. Moreover, induction of intercellular adhesion results in Rac activation, which can be blocked by pharmacological inhibitors of the EGF receptor, but not by inhibitors of phosphatidylinositol 3-kinase or MAPK.
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(2002)
J Biol Chem
, vol.277
, pp. 36962-36969
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Betson, M.1
Lozano, E.2
Zhang, J.3
Braga, V.M.4
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46
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0028170977
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β-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor
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Hoschuetzky H., Aberle H., Kemler R. β-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 127:1994;1375-1380.
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J Cell Biol
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Hoschuetzky, H.1
Aberle, H.2
Kemler, R.3
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47
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0031825437
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Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells
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Esser S., Lampugnani M.G., Corada M., Dejana E., Risau W. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci. 111:1998;1853-1865.
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J Cell Sci
, vol.111
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Esser, S.1
Lampugnani, M.G.2
Corada, M.3
Dejana, E.4
Risau, W.5
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48
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0036118004
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Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: A potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling
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This is the first demonstration that vascular endothelial growth factor (VEGF)-dependent tyrosine phosphorylation of VE-cadherin results in cadherin association with Shc. Phosphorylation of Shc on VEGF stimulation lasts longer in endothelial cells lacking VE-cadherin than in cells expressing it, suggesting that VE-cadherin plays a negative role in Shc phosphorylation by the VEGF receptor-2.
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Zanetti A., Lampugnani M.G., Balconi G., Breviario F., Corada M., Lanfrancone L., Dejana E. Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling. Arterioscler Thromb Vasc Biol. 22:2002;617-622 This is the first demonstration that vascular endothelial growth factor (VEGF)-dependent tyrosine phosphorylation of VE-cadherin results in cadherin association with Shc. Phosphorylation of Shc on VEGF stimulation lasts longer in endothelial cells lacking VE-cadherin than in cells expressing it, suggesting that VE-cadherin plays a negative role in Shc phosphorylation by the VEGF receptor-2.
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(2002)
Arterioscler Thromb Vasc Biol
, vol.22
, pp. 617-622
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Zanetti, A.1
Lampugnani, M.G.2
Balconi, G.3
Breviario, F.4
Corada, M.5
Lanfrancone, L.6
Dejana, E.7
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49
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0036121308
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Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
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The authors report the identification a new E3 ubiquitin ligase, called Hakai, that specifically interacts with E-cadherin in its tyrosine-phosphorylated form. Hakai induces E2-dependent ubiquitination of the E-cadherin complex in vitro and in vivo and promotes endocytosis of the E-cadherin-catenin complex, thus relating the activity of tyrosine kinases at cell-cell contacts with the degradation of junctional components and the consequent impairment of intercellular adhesion.
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Fujita Y., Krause G., Scheffner M., Zechner D., Leddy H.E., Behrens J., Sommer T., Birchmeier W. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol. 4:2002;222-231 The authors report the identification a new E3 ubiquitin ligase, called Hakai, that specifically interacts with E-cadherin in its tyrosine-phosphorylated form. Hakai induces E2-dependent ubiquitination of the E-cadherin complex in vitro and in vivo and promotes endocytosis of the E-cadherin-catenin complex, thus relating the activity of tyrosine kinases at cell-cell contacts with the degradation of junctional components and the consequent impairment of intercellular adhesion.
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(2002)
Nat Cell Biol
, vol.4
, pp. 222-231
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Fujita, Y.1
Krause, G.2
Scheffner, M.3
Zechner, D.4
Leddy, H.E.5
Behrens, J.6
Sommer, T.7
Birchmeier, W.8
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