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Role of protein kinase C in arginine vasopressin‐stimulated ERK and p70S6 kinase phosphorylation
Author(s) -
Ghosh Paramita M.,
Bedolla Roble,
Thomas Charles A.,
Kreisberg Jeffrey I.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10789
Subject(s) - protein kinase c , kinase , phosphorylation , biology , mapk/erk pathway , epidermal growth factor , protein kinase a , microbiology and biotechnology , biochemistry , receptor
We previously showed in rat renal glomerular mesangial cells, that arginine vasopressin (AVP)‐stimulated cell proliferation was mediated by epidermal growth factor receptor (EGF‐R) transactivation, and activation (phosphorylation) of ERK1/2 and p70S6 kinase (Ghosh et al. [2001]: Am J Physiol Renal Physiol 280:F972–F979]. In this paper, we extend these observations and show that different protein kinase C (PKC) isoforms play different roles in mediating AVP‐stimulated ERK1/2 and p70S6 kinase phosphorylation and cell proliferation. AVP treatment for 0–60 min stimulated the serine/threonine phosphorylation of PKC isoforms α, δ, ε, and ζ. The activation of PKC was dependent on EGF‐R and phosphatidylinositol 3‐kinase (PI3K) activation. In addition, inhibition of conventional and novel PKC isoforms by chronic (24 h) exposure to phorbol 12‐myristate 13‐acetate (PMA) inhibited AVP‐induced activation of ERK and p70S6 kinase as well as EGF‐R phosphorylation. Rottlerin, a specific inhibitor of PKCδ, inhibited both ERK and p70S6 kinase phosphorylation and cell proliferation. In contrast, a PKCε translocation inhibitor decreased ERK1/2 activation without affecting p70S6 kinase or cell proliferation, while a dominant negative PKCζ (K281W) cDNA delayed p70S6 kinase activation without affecting ERK1/2. On the other hand, Gö6976, an inhibitor of conventional PKC isoforms, did not affect p70S6 kinase, but stimulated ERK1/2 phosphorylation without affecting cell proliferation. Our results indicate that PKCδ plays an important role in AVP‐stimulated ERK and p70S6 kinase activation and cell proliferation. © 2004 Wiley‐Liss, Inc.