Gα12 Stimulates c-Jun NH2-terminal Kinase through the Small G Proteins Ras and Rac*

The pertussis toxin (PTX) insensitive heterotrimeric G protein G12 has been implicated in mitogenesis and transformation, but its direct effectors remain unknown. To define potential signaling pathways utilized by G12, we expressed an activated mutant of its α subunit, Gα12(Q229L), in HEK293 cells and examined its effects on Ras and mitogen-activated protein kinases (MAPKs). Transient expression of activated Gα12 increased the percentage of Ras in the active, GTP-bound state, stimulated c-Jun NH2-terminal kinase (JNK) activity, and enhanced the transcriptional activity of c-Jun. Dominant negative Ras (N17Ras) inhibited Gα12-mediated JNK activation in NIH3T3 cells but failed to do so in HEK293 cells. In contrast, dominant negative Rac (N17Rac1) inhibited JNK activation by Gα12 in HEK293 cells as well as three other cell lines. In 1321N1 cells, where thrombin stimulates G12-dependent mitogenesis, coexpression of N17Rac1 or a dominant negative mutant of MEKK1 (MEKKΔ(K432M)) inhibits c-Jun/AP-1 sensitive reporter gene expression stimulated by thrombin or Gα12. These data demonstrate that the α subunit of the heterotrimeric G protein G12, like tyrosine kinase growth factor receptors, activates Ras and recruits a signal transduction pathway involving the small GTP-binding protein Rac that leads to JNK activation.

• Publication year

  1996

• Venue

  Journal of Biological Chemistry

• Publication date

  1996-07-19

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.271.29.17349PMID 8663428
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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