| First Author | Baumeister U | Year | 2005 |
| Journal | EMBO J | Volume | 24 |
| Issue | 9 | Pages | 1686-95 |
| PubMed ID | 15861137 | Mgi Jnum | J:98324 |
| Mgi Id | MGI:3577866 | Doi | 10.1038/sj.emboj.7600647 |
| Citation | Baumeister U, et al. (2005) Association of Csk to VE-cadherin and inhibition of cell proliferation. EMBO J 24(9):1686-95 |
| abstractText | Vascular endothelial cadherin (VE-cadherin) mediates contact inhibition of cell growth in quiescent endothelial cell layers. Searching for proteins that could be involved in VE-cadherin signaling, we found the cytosolic C-terminal Src kinase (Csk), a negative regulator of Src family kinases. We show that Csk binds via its SH2 domain to the phosphorylated tyrosine 685 of VE-cadherin. VE-cadherin recruits Csk to cell contacts and both proteins can be co-precipitated from cell lysates of transfected cells and endothelial cells. Association of VE-cadherin and Csk in endothelial cells increased with increasing cell density. CHO cells expressing the tyrosine replacement mutant VE-cadherin-Y685F grow to higher cell densities than cells expressing wild-type VE-cadherin. Overexpression of Csk in these cells under an inducible promoter inhibits cell proliferation in the presence and absence of VE-cadherin, but not in the presence of VE-cadherin-Y685F. Reduction of Csk expression by RNA interference enhances endothelial cell proliferation. Our results suggest that the phosphorylated tyrosine residue 685 of VE-cadherin and probably the binding of Csk to this site are involved in inhibition of cell growth triggered by cell density. |
