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G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism.

Publication ,  Journal Article
van Biesen, T; Hawes, BE; Raymond, JR; Luttrell, LM; Koch, WJ; Lefkowitz, RJ
Published in: J Biol Chem
January 19, 1996

Mitogen-activated protein kinase (MAPK) is activated in response to both receptor tyrosine kinases and G-protein-coupled receptors. Recently, Gi-coupled receptors, such as the alpha 2A adrenergic receptor, were shown to mediate Ras-dependent MAPK activation via a pathway requiring G-protein beta gamma subunits (G beta gamma) and many of the same intermediates involved in receptor tyrosine kinase signaling. In contrast, Gq-coupled receptors, such as the M1 muscarinic acetylcholine receptor (M1AChR), activate MAPK via a pathway that is Ras-independent but requires the activity of protein kinase C (PKC). Here we show that, in Chinese hamster ovary cells, the M1AChR and platelet-activating factor receptor (PAFR) mediate MAPK activation via the alpha-subunit of the G(o) protein. G(o)-mediated MAPK activation was sensitive to treatment with pertussis toxin but insensitive to inhibition by a G beta gamma-sequestering peptide (beta ARK1ct). M1AChR and PAFR catalyzed G(o) alpha-subunit GTP exchange, and MAPK activation could be partially rescued by a pertussis toxin-insensitive mutant of G(o) alpha but not by similar mutants of Gi. G(o)-mediated MAPK activation was insensitive to inhibition by a dominant negative mutant of Ras (N17Ras) but was completely blocked by cellular depletion of PKC. Thus, M1AChR and PAFR, which have previously been shown to couple to Gq, are also coupled to G(o) to activate a novel PKC-dependent mitogenic signaling pathway.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 19, 1996

Volume

271

Issue

3

Start / End Page

1266 / 1269

Location

United States

Related Subject Headings

  • ras Proteins
  • Virulence Factors, Bordetella
  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Muscarinic
  • Receptors, G-Protein-Coupled
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • Protein Kinase C
 

Citation

APA
Chicago
ICMJE
MLA
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van Biesen, T., Hawes, B. E., Raymond, J. R., Luttrell, L. M., Koch, W. J., & Lefkowitz, R. J. (1996). G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism. J Biol Chem, 271(3), 1266–1269. https://doi.org/10.1074/jbc.271.3.1266
Biesen, T. van, B. E. Hawes, J. R. Raymond, L. M. Luttrell, W. J. Koch, and R. J. Lefkowitz. “G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism.J Biol Chem 271, no. 3 (January 19, 1996): 1266–69. https://doi.org/10.1074/jbc.271.3.1266.
van Biesen T, Hawes BE, Raymond JR, Luttrell LM, Koch WJ, Lefkowitz RJ. G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism. J Biol Chem. 1996 Jan 19;271(3):1266–9.
van Biesen, T., et al. “G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism.J Biol Chem, vol. 271, no. 3, Jan. 1996, pp. 1266–69. Pubmed, doi:10.1074/jbc.271.3.1266.
van Biesen T, Hawes BE, Raymond JR, Luttrell LM, Koch WJ, Lefkowitz RJ. G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel protein kinase C-dependent mechanism. J Biol Chem. 1996 Jan 19;271(3):1266–1269.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 19, 1996

Volume

271

Issue

3

Start / End Page

1266 / 1269

Location

United States

Related Subject Headings

  • ras Proteins
  • Virulence Factors, Bordetella
  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Muscarinic
  • Receptors, G-Protein-Coupled
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • Protein Kinase C