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Insulin-Induced Phosphorylation and Activation of Phosphodiesterase 3B in Rat Adipocytes: Possible Role for Protein Kinase B But Not Mitogen-Activated Protein Kinase or p70 S6 Kinase¹

Section for Molecular Signalling (J.W., T.R.L., P.B., E.D.), Department of Cell and Molecular Biology, Lund University, Sweden; and National Heart, Lung and Blood Institutes (V.M.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Eva Degerman, Section for Molecular Signalling, Department of Cell and Molecular Biology, University of Lund, P.O. Box 94, S-221 00 Lund, Sweden. E-mail: Eva.Degerman{at}medkem.lu.se

Insulin stimulation of adipocytes results in serine phosphorylation/activation of phosphodiesterase 3B (PDE 3B) and activation of a kinase that phosphorylates PDE 3B in vitro, key events in the antilipolytic action of this hormone. We have investigated the role for p70 S6 kinase, mitogen-activated protein kinases (MAP kinases), and protein kinase B (PKB) in the insulin signaling pathway leading to phosphorylation/activation of PDE 3B in adipocytes. Insulin stimulation of adipocytes resulted in increased activity of p70 S6 kinase, which was completely blocked by pretreatment with rapamycin. However, rapamycin had no effect on the insulin-induced phosphorylation/activation of PDE 3B or the activation of the kinase that phosphorylates PDE 3B. Stimulation of adipocytes with insulin or phorbol myristate acetate induced activation of MAP kinases. Pretreatment of adipocytes with the MAP kinase kinase inhibitor PD 98059 was without effect on the insulin-induced activation of PDE 3B. Furthermore, phorbol myristate acetate stimulation did not result in phosphorylation/activation of PDE 3B or activation of the kinase that phosphorylates PDE 3B. Using Mono Q and Superdex chromatography, the kinase that phosphorylates PDE 3B was found to co-elute with PKB, but not with p70 S6 kinase or MAP kinases. Furthermore, both PKB and the kinase that phosphorylates PDE 3B were found to translocate to membranes in response to peroxovanadate stimulation of adipocytes in a wortmannin-sensitive way.

Whereas these results suggest that p70 S6 kinase and MAP kinases are not involved in the insulin-induced phosphorylation/activation of PDE 3B in rat adipocytes, they are consistent with PKB being the kinase that phosphorylates PDE 3B.

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