Document Detail


Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
MedLine Citation:
PMID:  11972023     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In response to IFN-gamma, the latent cytoplasmic protein signal transducers and activators of transcription 1 (Stat1) becomes phosphorylated on Y701, dimerizes, and accumulates in the nucleus to activate transcription of IFN-gamma-responsive genes. For maximal gene activation, S727 in the transcription activation domain of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a group of nuclear proteins that interact specifically with the Stat1 transcription activation domain. In this report, we identified one of them as the multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1-dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by CaMKII. Thus two different cellular signaling events, IFN-gamma receptor occupation and Ca(2+) flux, are required for Stat1 to achieve maximal transcriptional activation through regulation of phosphorylation.
Authors:
Jayasree S Nair; Christopher J DaFonseca; Agneta Tjernberg; Wei Sun; James E Darnell; Brian T Chait; J Jillian Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-04-23
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  99     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-05-01     Completed Date:  2002-06-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5971-6     Citation Subset:  IM    
Affiliation:
Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Blotting, Western
Calcium / metabolism,  physiology*
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / physiology*
Cell Line
Cell Nucleus / metabolism
DNA-Binding Proteins / metabolism*
Dimerization
Glutathione Transferase / metabolism
Humans
Interferon-gamma / metabolism*
Mice
Phosphorylation
Precipitin Tests
Protein Binding
Protein Structure, Tertiary
Recombinant Fusion Proteins / metabolism
STAT1 Transcription Factor
Serine / chemistry*
Time Factors
Trans-Activators / metabolism*
Transcription, Genetic
Transcriptional Activation
Transfection
Grant Support
ID/Acronym/Agency:
AI31489/AI/NIAID NIH HHS; AI34420/AI/NIAID NIH HHS; GM61652/GM/NIGMS NIH HHS; RR00862/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Recombinant Fusion Proteins; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Stat1 protein, mouse; 0/Trans-Activators; 56-45-1/Serine; 7440-70-2/Calcium; 82115-62-6/Interferon-gamma; EC 2.5.1.18/Glutathione Transferase; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases
Comments/Corrections

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


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