Vascular endothelial growth factor induces activation and subcellular translocation of focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes

Vascular endothelial growth factor (VEGF) has been proposed to be among the candidate factors with the most potential to play a role in ischemia-induc ed collateral vessel formation, Recently, we found that VEGF activated the mitogen-activated protein kinase cascade in cultured rat cardiac myocytes, To elucidate how VEGF affects adhesive interaction of cardiac myocytes with the extracellular matrix (ECM), one of the important cell functions, we in vestigated the molecular mechanism of activation of focal adhesion-related proteins, especially focal adhesion kinase (p125(FAK)), in cultured rat car diac myocytes, We found that the 2 VEGF receptors, KDR/Flk-1 and Flt-1, wer e expressed in cardiac myocytes and that KDR/Flk-1 was significantly tyrosi ne phosphorylated on VEGF stimulation, VEGF induced tyrosine phosphorylatio n and activation of p125(FAK) as well as tyrosine phosphorylation of paxill in; this was accompanied by subcellular translocation of p125(FAK) from per inuclear sites to the focal adhesions. This VEGF-induced activation of p125 (FAK) was inhibited partially by the tyrosine kinase inhibitors genistein a nd tyrphostin, Activation of p125(FAK) was accompanied by its increased ass ociation with adapter proteins GRB2, Shc, and nonreceptor type tyrosine kin ase p60(c-src) Furthermore, we confirmed that VEGF induced a significant in crease in adhesive interaction between cardiac myocytes and ECM using an el ectric cell-substrate impedance sensor. These results strongly suggest that p125(FAK) is one of the most important components in VEGF-induced signalin g in cardiac myocytes, playing a critical role in adhesive interaction betw een cardiac myocytes and ECM.