FOCAL ADHESION KINASE IS ABUNDANT IN DEVELOPING BLOOD-VESSELS AND ELEVATION OF ITS PHOSPHOTYROSINE CONTENT IN VASCULAR SMOOTH-MUSCLE CELLS IS A RAPID RESPONSE TO ANGIOTENSIN-II

Focal adhesion kinase (FAK) is a structurally unique nonreceptor prote in-tyrosine kinase that localizes to focal adhesion plaques. Regulatio n of its activity has been implicated in diverse signaling pathways, i ncluding those mediated by extracellular matrix/integrin interactions, G-protein coupled receptors for mitogenic neuropeptides, and certain oncogene products. To gain evidence for specific processes in which FA K may be involved in vivo, a study was initiated to determine its expr ession pattern during mouse development. FAK expression was detected i n early embryos and appeared to be distributed throughout all cell typ es at about the time of neurulation. Subsequent to neural tube closure , expression became particularly abundant in the developing vasculatur e. This included expression in the medial layer of arteries populated by smooth muscle cells. In vitro studies using cultured rat aortic vas cular smooth muscle cells demonstrate that FAK phosphotyrosine content is dramatically elevated in response to plating cells onto the adhesi ve glycoprotein, fibronectin. Also, enhanced tyrosine phosphorylation of FAK is observed in these cells upon stimulation with the vasoconstr ictor angiotensin Il. Thus, in vascular smooth muscle cells, like fibr oblasts, FAK appears to play a role in signaling mechanisms induced by extracellular matrix components as well as G-protein coupled receptor agonists. The combined results of this study suggest that signaling t hrough FAK may play an important role in blood vessel morphogenesis an d function. (C) 1994 Wiley-Liss, Inc.