PMID- 10400692
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 29
DP  - 1999 Jul 16
TI  - Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen 
      synthase and phosphorylation of 4E-BP1 (PHAS-1).
PG  - 20611-8
AB  - The roles of Akt (protein kinase B) and the atypical lambda isoform of protein
      kinase C (PKClambda), 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 Lys179 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 PKClambda (lambdaDeltaNKD), which prevents
      insulin-induced activation of PKClambda, 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, lambdaDeltaNKD had
      no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that
      Akt, but not PKClambda, is required for insulin activation of glycogen synthase
      and for insulin-induced phosphorylation of 4E-BP1.
FAU - Takata, M
AU  - Takata M
AD  - Second Department of Internal Medicine, Kobe University School of Medicine, 7-5-1
      Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Ogawa, W
AU  - Ogawa W
FAU - Kitamura, T
AU  - Kitamura T
FAU - Hino, Y
AU  - Hino Y
FAU - Kuroda, S
AU  - Kuroda S
FAU - Kotani, K
AU  - Kotani K
FAU - Klip, A
AU  - Klip A
FAU - Gingras, A C
AU  - Gingras AC
FAU - Sonenberg, N
AU  - Sonenberg N
FAU - Kasuga, M
AU  - Kasuga M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Insulin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.4.1.11 (Glycogen Synthase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - *Carrier Proteins
MH  - Cell Line
MH  - Cricetinae
MH  - Enzyme Activation
MH  - Glycogen Synthase/*metabolism
MH  - Insulin/*pharmacology
MH  - Mutation
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
AID - 10.1074/jbc.274.29.20611 [doi]
AID - S0021-9258(19)72693-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 16;274(29):20611-8. doi: 10.1074/jbc.274.29.20611.