Hypoxia induces activation and subcellular translocation of focal adhesionkinase (p125(FAK)) in cultured rat cardiac myocytes

We previously reported that hypoxia caused rapid activation of RAS/mitogen- activated protein kinase (MAPK) pathway, two other stress-activated MAPK fa mily members, stress-activated protein kinase (SAPK) and p38MAPK, and Src f amily tyrosine kinases, p60(c-src) and p59(c-fyn) in cultured rat cardiac m yocytes. In this study, to elucidate how hypoxia affects adhesive interacti on between cardiac myocytes and extracellular matrix (ECM), we investigated the molecular mechanism of the activation of focal adhesion-associated tyr osine kinases p125(FAK) and paxillin. Here, we show that hypoxia induced ty rosine phosphorylation of p125(FAK) and paxillin and that hypoxia-induced a ctivation of p125(FAK) was accompanied by its increased association with ad apter proteins Shc and GRB2, and non-receptor type tyrosine kinase p60(c-sr c). Furthermore, hypoxia caused subcellular translocation of p125(FAK) from perinuclear sites to the focal adhesions. These results strongly suggest t hat p125(FAK) is one of the most important components in hypoxia-induced in tracellular signaling in cardiac myocytes and may play a pivotal role in ad hesive interaction between cardiac myocytes and ECM. (C) 1999 Academic Pres s.