Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB.
Proc Natl Acad Sci U S A
; 108(4): 1391-6, 2011 Jan 25.
Article
in En
| MEDLINE
| ID: mdl-21220345
ABSTRACT
The second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)), formed by the p110 family of PI3-kinases, promotes cellular growth, proliferation, and survival, in large part by activating the protein kinase Akt/PKB. We show that inositol polyphosphate multikinase (IPMK) physiologically generates PIP(3) as well as water soluble inositol phosphates. IPMK deletion reduces growth factor-elicited Akt signaling and cell proliferation caused uniquely by loss of its PI3-kinase activity. Inhibition of p110 PI3-kinases by wortmannin prevents IPMK phosphorylation and activation. Thus, growth factor stimulation of Akt signaling involves PIP(3) generation through the sequential activations of the p110 PI3-kinases and IPMK. As inositol phosphates inhibit Akt signaling, IPMK appears to act as a molecular switch, inhibiting or stimulating Akt via its inositol phosphate kinase or PI3-kinase activities, respectively. Drugs regulating IPMK may have therapeutic relevance in influencing cell proliferation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphotransferases (Alcohol Group Acceptor)
/
Phosphatidylinositol 3-Kinases
/
Proto-Oncogene Proteins c-akt
/
Fibroblasts
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
/
Male
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2011
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA