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Activated mutant of Gα 12 enhances the hyperosmotic stress response of NIH3T3 cells
Author(s) -
Dermott Jonathan M.,
Wadsworth Sandra J.,
van Rossum George D. V.,
Dhanasekaran N.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20010401)81:1<1::aid-jcb1019>3.0.co;2-v
Subject(s) - osmotic concentration , microbiology and biotechnology , heterotrimeric g protein , osmotic shock , mutant , cell culture , kinase , chemistry , signal transduction , biology , g protein , biochemistry , genetics , gene
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 Gα 12 (Gα 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 Gα 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 Gα 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 μM dimethylamiloride potently inhibited their hyperosmotic response whereas the response was only partially inhibited in Gα 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 Gα 12 can enhance this response by modulating either or both of these components namely, JNKs and NHEs in NIH3T3 cells. J. Cell. Biochem. 81:1–8, 2001. © 2001 Wiley‐Liss, Inc.