Document Detail


Requirement for phosphatidylinositol-3 kinase activity during progression through S-phase and entry into mitosis.
MedLine Citation:
PMID:  12742227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatidylinositol-3 kinase (PI3K) proteins are important regulators of cell survival and proliferation. PI3K-dependent signalling regulates cell proliferation by promoting G1- to S-phase progression during the cell cycle. However, a definitive role for PI3K at other times during the cell cycle is less clear. In these studies, we provide evidence that PI3K activity is required during DNA synthesis (S-phase) and G2-phase of the cell cycle. Inhibition of PI3K with LY294002 at the onset of S-phase caused a 4- to 5-h delay in progression through G2/M. LY294002 treatment at the end of S-phase caused an approximate 2-h delay in progression through G2/M, indicating that PI3K activity functions for both S- and G2-phase progression. The expression of constitutively activated Akt partially reversed the inhibitory effects of LY294002 on mitotic entry, which demonstrated that Akt was one PI3K target that was required during G2/M transitions. Inhibition of PI3K resulted in enhanced susceptibility of G2/M synchronized cells to undergo apoptosis in response to DNA damage as compared to asynchronous cells. Thus, similar to its role in promoting cell survival and cell cycle transitions from G1 to S phase, PI3K activity appears to promote entry into mitosis and protect against cell death during S- and G2-phase progression.
Authors:
Surabhi Dangi; Hyukjin Cha; Paul Shapiro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular signalling     Volume:  15     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-05-13     Completed Date:  2004-02-19     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  667-75     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology
Cell Cycle Proteins / metabolism
Chromones / pharmacology*
DNA Damage / physiology
Enzyme Inhibitors / pharmacology*
G2 Phase / physiology
HeLa Cells
Humans
Mitosis / physiology*
Morpholines / pharmacology*
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism*
Phosphorylation
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
S Phase / physiology*
cdc25 Phosphatases / metabolism
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Chromones; 0/Enzyme Inhibitors; 0/Morpholines; 0/Proto-Oncogene Proteins; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/CDC25C protein, human; EC 3.1.3.48/cdc25 Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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