pp60(c-src) modulates microvascular endothelial phenotype and in vitro angiogenesis.
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.
Marx
M
M
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Warren
S L
SL
Madri
J A
JA
D000273:Adipose Tissue / Q000098:blood supply*; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016391:Genes, src; D005822:Genetic Vectors; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008979:Moloney murine leukemia virus; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D016392:Proto-Oncogene Proteins pp60(c-src)