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J Biol Chem. 1998 Oct 2;273(40):25770-6.

The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells.

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  • 1Department of Experimental Pathology, The Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.


Cortactin, a filamentous actin cross-linking protein and a substrate of Src protein tyrosine kinase, is phosphorylated at tyrosine residues upon stimulation by extracellular signals. We have previously demonstrated that the filamentous actin cross-linking activity of cortactin is attenuated by Src (Huang, C., Ni, Y., Gao, Y., Haudenschild, C. C., and Zhan, X. (1997) J. Biol. Chem. 272, 13911-13915). In vitro, tyrosine phosphorylation of cortactin occurs specifically within the region between the proline-rich sequence and the Src homology 3 domain. Among the nine tyrosine residues in this region, mutations at Tyr421, Tyr466, and Tyr482 significantly reduced Src-meditated tyrosine phosphorylation both in vitro and in vivo. Ectopic expression of wild-type cortactin in ECV304, a spontaneously transformed human umbilical endothelial cell line, resulted in an enhanced cell migration. In contrast, overexpression of a cortactin mutant deficient in tyrosine phosphorylation impaired the migration of endothelial cells. These findings reveal an intracellular signaling mechanism whereby the motility of endothelial cells is regulated by a Src-mediated tyrosine phosphorylation of cortactin.

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