Document Detail

Activated mutant of Galpha(12) enhances the hyperosmotic stress response of NIH3T3 cells.
MedLine Citation:
PMID:  11180393     Owner:  NLM     Status:  MEDLINE    
Heterotrimeric G protein G12 stimulates diverse physiological responses including the activities of Na+/H+ exchangers and Jun kinases. We have observed that the expression of the constitutively activated, GTPase-deficient mutant of Galpha(12) (Galpha(12)QL) accelerates the hyperosmotic response of NIH3T3 cells as monitored by the hyperosmotic stress-stimulated activity of JNK1. The accelerated response appears to be partly due to the increased basal activity of JNK since cell lines-such as NIH3T3 cells expressing JNK1-in which JNK activity is elevated, show a similar response. NIH3T3 cells expressing Galpha(12)QL also display heightened sensitivity to hyperosmotic stress. This is in contrast to JNK1-NIH3T3 cells that failed to enhance sensitivity although they do exhibit an accelerated hyperosmotic response. Reasoning that the increased sensitivity seen in Galpha(12)QL cells is due to a signaling component other than JNK, the effect of dimethyamiloride, an inhibitor of Na+/H+ exchanger in this response, was assessed. Treatment of vector control NIH3T3 cells with 50 microM dimethylamiloride potently inhibited their hyperosmotic response whereas the response was only partially inhibited in Galpha(12)QL-NIH3T3 cells. These results, for the first time, identify that NHEs are upstream of the JNK module in the hyperosmotic stress-signaling pathway and that Galpha(12) can enhance this response by modulating either or both of these components namely, JNKs and NHEs in NIH3T3 cells.
J M Dermott; S J Wadsworth; G D van Rossum; N Dhanasekaran
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  81     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2001  
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Fels Institute for Cancer Research and Molecular Biology, Temple University, School of Medicine, Philadelphia, PA 19140, USA.
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MeSH Terms
3T3 Cells
Heterotrimeric GTP-Binding Proteins / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases / metabolism
Osmotic Pressure
Grant Support
Reg. No./Substance:
EC Mitogen-Activated Protein Kinases; EC Protein Kinases; EC GTP-Binding Proteins

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

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