Stimulation of 90-and 70-kDa ribosomal protein S6 kinases by arginine vasopressin and lysophosphatidic acid in rat cardiomyocytes

Arginine vasopressin (AVP) and lysophosphatidic acid (LPA) have been shown to stimulate protein kinase C (PKC) and mitogen-activated protein (MAP) kin ases and the proliferation of vascular smooth muscle cells. However, the ac tions of these two agents in cardiomyocytes are less well understood. To in vestigate the signal transduction pathways of AVP and LPA, freshly isolated adult rat cardiomyocytes were examined. Both AVP and LPA induced concentra tion- and time-dependent stimulation of the phosphotransferase activities o f p90 ribosomal S6 kinases (RSK) and their upstream activators, extracellul arly regulated kinases (ERK) 1 and 2. The activation of ERK1 and ERK2 by LP A was PKC- and phosphatidylinositol 3-kinase (PI 3-kinase)-dependent. Howev er, AVP-induced activation of RSK2, a downstream substrate of ERK1 and ERK2 , was PKC-dependent and PI 3-kinase-independent. AVP and LPA were also obse rved to increase the phosphotransferase activity of p70 ribosomal protein S 6 kinase (p70 S6K) in a time- and concentration-dependent manner. The activ ation of p70 S6K by LPA and AVP was PI 3-kinase-dependent. PKC was necessar y in AVP- but nut in LPA-induced activation of p70 S6K. Since RSK and p70 S 6K have been implicated in the regulation of translational control of prote in synthesis, we concluded that AVP and LPA may stimulate the growth of car diomyocytes through these two protein kinase cascades. (C) 2000 Elsevier Sc ience Inc.