PMID- 12897244
OWN - NLM
STAT- MEDLINE
DCOM- 20031029
LR  - 20211203
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 100
IP  - 17
DP  - 2003 Aug 19
TI  - The phosphatidylinositol (PI)-5-phosphate 4-kinase type II enzyme controls 
      insulin signaling by regulating PI-3,4,5-trisphosphate degradation.
PG  - 9867-72
AB  - Phosphatidylinositol-5-phosphate (PI-5-P) is a newly identified phosphoinositide 
      with characteristics of a signaling lipid but no known cellular function. PI-5-P 
      levels are controlled by the type II PI-5-P 4-kinases (PIP4K IIs), a family of 
      kinases that converts PI-5-P into phosphatidylinositol-4,5-bisphosphate 
      (PI-4,5-P2). The PI-5-P pathway is an alternative route for PI-4,5-P2 synthesis 
      as the bulk of this lipid is generated by the canonical pathway in which 
      phosphatidylinositol-4-phosphate (PI-4-P) is the intermediate. Here we examined 
      the effect of activation of the PI-5-P pathway on phosphoinositide 3-kinase 
      (PI3K) signaling by expressing PIP4K II beta in cells that lack this enzyme. 
      Although PIP4K II generates PI-4,5-P2, a substrate for PI3K, expression of this 
      enzyme reduced rather than increased phosphatidylinositol-3,4,5-trisphosphate 
      (PI-3,4,5-P3) levels in cells stimulated with insulin or cells expressing 
      activated PI3K. This reduction in PI-3,4,5-P3 levels resulted in decreased 
      activation of the downstream protein kinase, Akt/PKB. Consistent with these 
      results, expression of IpgD, a bacterial phosphatase that converts PI-4,5-P2 to 
      PI-5-P, resulted in Akt activation, and this effect was partially reversed by 
      PIP4K II beta. PIP4K II beta expression did not impair insulin-dependent 
      association of PI3K with insulin receptor substrate 1 (IRS1) but abbreviated Akt 
      activation, indicating that PIP4K II regulates PI-3,4,5-P3 degradation rather 
      than synthesis. These data support a model in which the PI-5-P pathway controls 
      insulin signaling that leads to Akt activation by regulating a PI-3,4,5-P3 
      phosphatase.
FAU - Carricaburu, Valerie
AU  - Carricaburu V
AD  - Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.
FAU - Lamia, Katja A
AU  - Lamia KA
FAU - Lo, Elizabeth
AU  - Lo E
FAU - Favereaux, Laetitia
AU  - Favereaux L
FAU - Payrastre, Bernard
AU  - Payrastre B
FAU - Cantley, Lewis C
AU  - Cantley LC
FAU - Rameh, Lucia E
AU  - Rameh LE
LA  - eng
GR  - GM 36624/GM/NIGMS NIH HHS/United States
GR  - R01 GM036624/GM/NIGMS NIH HHS/United States
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
GR  - R01 GM041890/GM/NIGMS NIH HHS/United States
GR  - 5P30 DK 36836-15/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 - 20030801
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bacterial Proteins)
RN  - 0 (Insulin)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 0 (phosphatidylinositol 5-phosphate)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.- (IpgD protein, Shigella flexneri)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/metabolism
MH  - CHO Cells
MH  - COS Cells
MH  - Cricetinae
MH  - Down-Regulation
MH  - Humans
MH  - Insulin/*metabolism
MH  - Models, Biological
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphatidylinositol Phosphates/*metabolism
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/classification/genetics/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptor, Insulin/genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Shigella flexneri/enzymology/genetics
MH  - Signal Transduction
PMC - PMC187868
EDAT- 2003/08/05 05:00
MHDA- 2003/10/30 05:00
PMCR- 2004/02/19
CRDT- 2003/08/05 05:00
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2003/10/30 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
PHST- 2004/02/19 00:00 [pmc-release]
AID - 1734038100 [pii]
AID - 1009867 [pii]
AID - 10.1073/pnas.1734038100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9867-72. doi: 
      10.1073/pnas.1734038100. Epub 2003 Aug 1.