Requirement for Akt (Protein Kinase B) in Insulin-induced Activation of Glycogen Synthase and Phosphorylation of 4E-BP1 (PHAS-1)

• Published in: The Journal of biological chemistry Vol. 274; no. 29; pp. 20611 - 20618
• Main Authors: Takata, M, Ogawa, W, Kitamura, T, Hino, Y, Kuroda, S, Kotani, K, Klip, A, Gingras, A C, Sonenberg, N, Kasuga, M
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 16.07.1999
• Subjects: Amino Acid Sequence; Animals; Carrier Proteins; Cell Line; CHO Cells; Cricetinae; Enzyme Activation; Glycogen Synthase - metabolism; Insulin - pharmacology; Mutation; Phosphoproteins - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.29.20611

The roles of Akt (protein kinase B) and the atypical λ isoform of protein kinase C (PKCλ), both of which act downstream of phosphoinositide 3-kinase, in the activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1) in response to insulin were investigated. A mutant Akt (Akt-AA) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin-induced activation of both Akt and glycogen synthase in L6 myotubes. Expression of a mutant Akt in which Lys 179 in the kinase domain was replaced by aspartate also inhibited insulin-induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt. A kinase-defective mutant of PKCλ (λΔNKD), which prevents insulin-induced activation of PKCλ, did not affect the activation of glycogen synthase by insulin. Insulin-induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells. However, λΔNKD had no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that Akt, but not PKCλ, is required for insulin activation of glycogen synthase and for insulin-induced phosphorylation of 4E-BP1.