Direct evidence for tyrosine and threonine phosphorylation and activation of mitogen-activated protein kinase by vasopressin in cultured rat vascular smooth muscle cells.

Mitogen-activated protein (MAP) kinases are members of a 40-45-kDa family of serine/threonine protein kinases that phosphorylate several substrates including microtubule-associated protein-2, S6 kinase, and myelin basic protein. Activity of MAP kinases is regulated by growth factors that stimulate the phosphorylation of threonine 188 and tyrosine 190 in the kinase. In this paper direct evidence is presented for tyrosine and threonine phosphorylation of MAP kinase in concert with elevated activity in response to vasopressin in primary cultures of vascular smooth muscle cells. Activation of MAP kinase is correlated with activation of S6 kinase activity related to S6 kinase II. Data support the concept that the activation of MAP kinase by vasopressin is mediated by pertussis toxin-independent biochemical pathways.