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Exp Mol Pathol. 2001 Jun;70(3):201-13.

pp60(c-src) modulates microvascular endothelial phenotype and in vitro angiogenesis.

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Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.


The tyrosine kinase c-src associates with the platelet-derived growth factor (PDGF) receptor. Overexpression of wild-type c-src, a kinase-negative c-src mutant, and v-src in microvascular endothelial cells modulated the mitogenic effect of PDGF, suggesting that c-src kinase activity inhibits PDGF signals. Analyses of cell morphology in two-dimensional culture revealed changes in cell shape and size induced by the overexpression of c-src proteins. Investigations in three-dimensional culture unveiled a modulatory role of c-src during in vitro angiogenesis. Overexpression of c-src resulted in an increased diameter of tube-like structures, and the number of branching segments was decreased. Expression of the kinase-negative c-src mutant resulted in abortive tube formation consisting of disconnected multicellular fragments. These results indicate that the c-src tyrosine kinase exerts regulatory effects on endothelial proliferation, size, and cytoskeletal organization in two-dimensional culture and on the formation of a differentiated multicellular network in three-dimensional culture.

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