PMID- 15256535
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20211203
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 18
IP  - 10
DP  - 2004 Oct
TI  - Tissue-specific differences in activation of atypical protein kinase C and 
      protein kinase B in muscle, liver, and adipocytes of insulin receptor substrate-1 
      knockout mice.
PG  - 2513-21
AB  - Insulin receptor substrates (IRSs) 1 and 2 are postulated to control the 
      activation of phosphatidylinositol 3-kinase (PI3K)-dependent signaling factors, 
      namely, atypical protein kinase C (aPKC) and protein kinase B (PKB)/Akt, which 
      mediate metabolic effects of insulin. However, it is uncertain whether aPKC and 
      PKB are activated together or differentially in response to IRS-1 and IRS-2 
      activation in insulin-sensitive tissues. Presently, we examined insulin 
      activation of aPKC and PKB in vastus lateralis muscle, adipocytes, and liver in 
      wild-type and IRS-1 knockout mice, and observed striking tissue-specific 
      differences. In muscle of IRS-1 knockout mice, the activation of both aPKC and 
      PKB was markedly diminished. In marked contrast, only aPKC activation was 
      diminished in adipocytes, and only PKB activation was diminished in liver. These 
      results suggest that IRS-1 is required for: 1) activation of both aPKC and PKB in 
      muscle; 2) aPKC, but not PKB, activation in adipocytes; and 3) PKB, but not aPKC, 
      activation in liver. Presumably, IRS-2 or other PI3K activators account for the 
      normal activation of aPKC in liver and PKB in adipocytes of IRS-1 knockout mice. 
      These complexities in aPKC and PKB activation may be relevant to metabolic 
      abnormalities seen in tissues in which IRS-1 or IRS-2 is specifically or 
      predominantly down-regulated.
FAU - Sajan, Mini P
AU  - Sajan MP
AD  - Research Service, James A. Haley Veterans Hospital and the Department of Internal 
      Medicine, University of South Florida College of Medicine, Tampa, Florida 33612, 
      USA.
FAU - Standaert, Mary L
AU  - Standaert ML
FAU - Miura, Atsushi
AU  - Miura A
FAU - Kahn, C Ron
AU  - Kahn CR
FAU - Farese, Robert V
AU  - Farese RV
LA  - eng
GR  - R01 DK065969/DK/NIDDK NIH HHS/United States
GR  - DK-38079-09A1/DK/NIDDK NIH HHS/United States
GR  - DK33201/DK/NIDDK NIH HHS/United States
GR  - DK55545/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040715
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs2 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Adipocytes/enzymology/physiology
MH  - Animals
MH  - Enzyme Activation
MH  - Insulin Receptor Substrate Proteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Liver/enzymology/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Skeletal/enzymology/physiology
MH  - Phosphoproteins/genetics/*physiology
MH  - Protein Kinase C/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Sequence Deletion
MH  - Signal Transduction
EDAT- 2004/07/17 05:00
MHDA- 2005/03/04 09:00
CRDT- 2004/07/17 05:00
PHST- 2004/07/17 05:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/07/17 05:00 [entrez]
AID - me.2004-0045 [pii]
AID - 10.1210/me.2004-0045 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2004 Oct;18(10):2513-21. doi: 10.1210/me.2004-0045. Epub 2004 Jul 
      15.