MITOGEN-ACTIVATED PROTEIN-KINASES MEDIATE CHANGES IN GENE-EXPRESSION,BUT NOT CYTOSKELETAL ORGANIZATION ASSOCIATED WITH CARDIAC-MUSCLE CELLHYPERTROPHY

Shortly after birth, cardiac myocytes lose the ability to divide, and, in adult animals, heart muscle grows by a process of cellular hypertr ophy where each individual cell gets larger. We have previously shown that activated Pas protein can induce markers of the hypertrophic phen otype, including atrial natriuretic factor (ANF) expression and organi zation of contractile proteins, and that Pas is at least partially req uired for the hypertrophic effect of phenylephrine. In the present stu dy, we examine the requirement for the mitogen-activated protein kinas es (MAP kinases) in the hypertrophic response induced by phenylephrine . We find that phenylephrine treatment results in the activation of th e MAP kinases and that this activity is required for transactivation o f the fos, ANF, and MLH promoters. However, inhibition of MAP kinases does not prevent phenylephrine-induced organization of actin. These re sults suggest that the signal transduction pathways leading to differe nt hypertrophic responses diverge upstream of the MAP kinases but poss ibly downstream of Pas.