Journal of Biological Chemistry
Volume 270, Issue 31, 4 August 1995, Pages 18655-18659
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Cell Biology and Metabolism
Activation of Jun Kinase/Stress-activated Protein Kinase by GTPase-deficient Mutants of Gα12 and Gα13*

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Signal transduction pathways regulated by G12 and G13 heterotrimeric G proteins are largely unknown. Expression of activated, GTPase-deficient mutants of α12 and α13 alter physiological responses such as Na+/H+ exchanger activity, but the effector pathways controlling these responses have not been defined. We have found that the expression of GTPase-deficient mutants of α1212Q229L) or α1313Q226L) leads to robust activation of the Jun kinase/stress-activated protein kinase (JNK/SAPK) pathway. Inducible α12Q229L and α13Q226L expression vectors stably transfected in NIH 3T3 cells demonstrated JNK/SAPK activation but not extracellular response/mitogen-activated protein kinase activation. Transient transfection of α12Q229L and α13Q226L also activated the JNK/SAPK pathway in COS-1 cells. Expression of the GTPase-deficient mutant of αqqQ209L) but not αiiQ205L) or αssQ227L) was also able to activate the JNK/SAPK pathway. Functional Ras signaling was required for α12Q229L and α13Q226L activation of the JNK/SAPK pathway; expression of competitive inhibitory N17Ras inhibited JNK/SAPK activation in response to both α12Q229L and α13Q226L. The results describe for the first time a Ras-dependent signal transduction pathway involving JNK/SAPK regulated by α12 and α13.

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This work was supported by NCI Core Program on Carcinogenesis Grant 5-P30-CA 12227 (to N. D.) and National Institutes of Health Grants GM 30324, CA 58187, and DK 37871 (to G. L. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Contributed equally to this paper.