Focal adhesion kinase is involved in angiotensin II-mediated protein synthesis in cultured vascular smooth muscle cells

The rate of vascular smooth muscle cell protein synthesis and cellular hype rtrophy in response to angiotensin II (Ang II) is dependent on activation o f protein tyrosine kinases (PTKs) and both the extracellular signal-regulat ed kinase (ERK) 1/2 and p70(S6K) pathways. One potential PTK that may regul ate these signaling cascades is focal adhesion kinase (FAK), a nonreceptor PTK associated with focal adhesions. We used an actin depolymerizing agent, cytochalasin D (Cyt-D), and a replication-defective adenovirus encoding FA K-related nonkinase (FRNK), an inhibitor of FAK-dependent signaling, as too ls to assess whether FAK was upstream of the ERK1/2 and/or the p70(S6K) pat hways. Cyt-D reduced basal FAK phosphorylation and blocked Ang II-dependent FAK phosphorylation in a dose-dependent manner. Confocal microscopy indica ted that Cyt-D induced actin filament disruption and FAK delocalization fro m focal adhesions. Cyt-D also reduced Ang II-induced ERK1/2 activation, but p70(S6K) activation was relatively unaffected. Cyt-D reduced basal protein synthetic rate and substantially reduced the Ang II-induced increase in pr otein synthesis. Similarly, FRNK overexpression blocked Ang II-induced FAK phosphorylation and ERK1/2 activation, but not p70S6K phosphorylation, and markedly inhibited protein synthesis. This is the first report to demonstra te that FAK is a critical component of the signal transduction pathways tha t mediate Ang II-induced ERK1/2 activation, c-fos induction, and enhanced p rotein synthesis in vascular smooth muscle cells.