Rk. Malik et Jt. Parsons, INTEGRIN-DEPENDENT ACTIVATION OF THE P70 RIBOSOMAL S6 KINASE SIGNALING PATHWAY, The Journal of biological chemistry, 271(47), 1996, pp. 29785-29791
Interaction of the cell surface integrin receptors with extracellular
matrix proteins results in the activation of intracellular signaling p
athways, including activation of the p42/p44 mitogen-activated protein
kinases. The protein tyrosine kinase focal adhesion kinase, or FAK, i
s linked to integrin signaling and interacts with several molecules in
volved in signal transduction, Here we report that exposure of fibrobl
ast cells to extracellular matrix proteins activates the p70/p85 ribos
omal S6 kinase (S6K) pathway in a ligand dependent manner. Treatment o
f cells with inhibitors of phosphatidylinositol 3-kinase, or FRAP (FKB
P 12/rapamycin-associated protein) blocks integrin-mediated activation
of S6K. In contrast to the integrin-directed activation of the mitoge
n-activated protein kinases, cytochalasin D treatment does not inhibit
S6K activation, Treatment with the protein tyrosine kinase inhibitors
herbimycin A and genistein completely blocks S6K activation, indicati
ng a requirement for tyrosine kinase activity. Overexpression of the C
OOH-terminal noncatalytic domain of FAK, FRNK (FAK-related non-kinase)
in chick embryo cells results in a significant reduction in the integ
rin-mediated activation of S6K and a concomitant reduction in FAK tyro
sine phosphorylation, These results indicate at least a partial requir
ement for FAK in the S6K activation pathway.