PMID- 10329640
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 21
DP  - 1999 May 21
TI  - Insulin activates the alpha isoform of class II phosphoinositide 3-kinase.
PG  - 14529-32
AB  - The novel class II phosphoinositide (PI) 3-kinases are characterized by the
      presence of a C-terminal C2 domain, but little is known about their regulation.
      We find insulin causes a rapid 2-3-fold increase in the activity of PI 3-kinase
      C2alpha (PI3K-C2alpha) in CHO-IR cells, 3T3-L1 adipocytes, and fully
      differentiated L5L6 myotubes. No insulin-induced activation of PI3K-C2alpha was
      observed in cell types known to have low responsiveness to insulin including HEK 
      293 cells, 3T3-L1 preadipocytes, and undifferentiated L5L6 myoblasts. The
      mechanism of activation of PI3K-C2alpha by insulin differs from that of class Ia 
      PI 3-kinases in that insulin stimulation did not cause PI3K-C2alpha to associate 
      with IRS-1 or insulin receptor. PI3K-C2alpha existed as a doublet, and insulin
      stimulation caused a redistribution from the lower molecular weight band to the
      higher molecular weight band, suggesting phosphorylation-induced bandshift.
      Consistent with this, in vitro phosphatase treatment reduced the intensity of the
      upper band back to that seen in unstimulated cells. This suggests that
      insulin-induced phosphorylation could play a role in regulation of the activity
      of PI3K-C2alpha. The finding that insulin activates PI3K-C2alpha in cell types
      known to possess a wide range of responses to insulin suggests that PI3K-C2alpha 
      is a novel component of insulin-stimulated signaling cascades.
FAU - Brown, R A
AU  - Brown RA
AD  - Department of Biochemistry and Molecular Biology, University College London,
      Gower Street, London WC1E 6BT, United Kingdom.
FAU - Domin, J
AU  - Domin J
FAU - Arcaro, A
AU  - Arcaro A
FAU - Waterfield, M D
AU  - Waterfield MD
FAU - Shepherd, P R
AU  - Shepherd PR
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 (Insulin)
RN  - 0 (Protein Isoforms)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Insulin/*physiology
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Isoforms
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1074/jbc.274.21.14529 [doi]
AID - S0021-9258(19)73121-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 21;274(21):14529-32. doi: 10.1074/jbc.274.21.14529.