INACTIVATION OF KINASE CASCADES IN MESANGIAL CELLS GROWN ON COLLAGEN TYPE-I

Growth on collagen type I gels is known to suppress the mitogenic resp onsiveness of mesangial cells. Because these cells proliferate in some renal diseases and themselves synthesize collagen type I, we examined the influence elf growth on collagen upon several kinase signaling ca scades involved in mesangial cell proliferation. Quiescent mesangial c ells grown on collagen type I and then stimulated with serum showed a markedly diminished induction of the protooncogene c-fos, compared wit h their counterparts on plastic or fibronectin. This effect was accomp anied by decreased activation of mitogen-activated (Erk family) and Ca 2+/calmodulin-dependent protein kinases. Cells on collagen showed lowe r basal protein kinase C (PKC) activity and diminished levels of PKC-a lpha and -zeta isoforms. Global phosphorylation of tyrosine residues w as diminished on collagen, and tyrosine phosphorylation of Erk and foc al adhesion kinase in response to serum was not detected, in contrast to cells on plastic. We conclude that attachment of mesangial cells to collagen type I results in a broad suppression of protein phosphoryla tion that is reflected in diminished induction of the c-fos gene and p robably underlies the conversion of cultured mesangial cells to a nonp roliferative phenotype.