PROTEIN-KINASE-C MODULATION OF FIBRONECTIN MATRIX ASSEMBLY

Fibroblasts have cell surface sites that mediate the assembly of fibro nectin (Fn) into the extracellular matrix. Treatment of fibroblasts wi th kinase inhibitors (ML-7, H7, HA1004, calphostin C, and staurosporin e) resulted in the rapid decrease in the binding of I-125-labeled plas ma Fn and iodinated amino-terminal fragments of Fn. The dose responses of the four inhibitors suggest that the target kinase is protein kina se C (PKC) rather than the cyclic AMP- or cyclic GMP-dependent kinases . Three different fibroblastic cells were similarly affected. The inhi bition was rapid and reversible and could not be overcome by increasin g concentrations of Fn. Treatment of fibroblasts with phorbol esters a nd other agents that activate PKC resulted in increased amounts of I-1 25-labeled Fn binding to the cell surface. These results imply that Fn matrix assembly is modulated by PKC-mediated phosphorylation.