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G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors.

Publication ,  Journal Article
Luttrell, LM; van Biesen, T; Hawes, BE; Koch, WJ; Krueger, KM; Touhara, K; Lefkowitz, RJ
Published in: Adv Second Messenger Phosphoprotein Res
1997

G-protein-coupled receptors that mediate cellular responses to a variety of humoral, endothelial-, or platelet-derived substances are able to stimulate MAP kinase activity. In transfected model systems, G-protein-coupled receptors that couple to pertussis toxin-insensitive G proteins of the Gq/11 family mediate this activation predominantly via a PKC-dependent mechanism. In contrast, activation of MAP kinase by receptors that couple to pertussis toxin-sensitive Gi proteins is PKC-independent and requires downstream activation of the low-molecular-weight G protein, Ras. This pathway can be inhibited by coexpression of peptides that sequester Gbetagamma subunits, and is mimicked by overexpression of Gbetagamma subunits. This Ras-dependent MAP kinase activation requires tyrosine phosphorylation of "docking proteins," including the shc adapter protein, and depends upon recruitment of Grb2/Sos1 complexes to the plasma membrane, thus resembling the pathway of MAP kinase activation employed by the receptor tyrosine kinases. Other molecules, including PI-3-kinases and phosphotyrosine phosphatases, probably also contribute to Gbetagamma-subunit-mediated assembly of a mitogenic signaling complex. Identification of the G-protein-coupled, receptor-regulated tyrosine kinase(s), and the means by which the mitogenic signaling complex is assembled at the plasma membrane, remain subjects of further study.

Duke Scholars

Published In

Adv Second Messenger Phosphoprotein Res

ISSN

1040-7952

Publication Date

1997

Volume

31

Start / End Page

263 / 277

Location

United States

Related Subject Headings

  • ras Proteins
  • Tyrosine
  • Signal Transduction
  • Receptors, Cell Surface
  • Phosphorylation
  • Phosphoproteins
  • Humans
  • GTP-Binding Proteins
  • Enzyme Activation
  • Calcium-Calmodulin-Dependent Protein Kinases
 

Citation

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Luttrell, L. M., van Biesen, T., Hawes, B. E., Koch, W. J., Krueger, K. M., Touhara, K., & Lefkowitz, R. J. (1997). G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors. Adv Second Messenger Phosphoprotein Res, 31, 263–277.
Luttrell, L. M., T. van Biesen, B. E. Hawes, W. J. Koch, K. M. Krueger, K. Touhara, and R. J. Lefkowitz. “G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors.Adv Second Messenger Phosphoprotein Res 31 (1997): 263–77.
Luttrell LM, van Biesen T, Hawes BE, Koch WJ, Krueger KM, Touhara K, et al. G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors. Adv Second Messenger Phosphoprotein Res. 1997;31:263–77.
Luttrell, L. M., et al. “G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors.Adv Second Messenger Phosphoprotein Res, vol. 31, 1997, pp. 263–77.
Luttrell LM, van Biesen T, Hawes BE, Koch WJ, Krueger KM, Touhara K, Lefkowitz RJ. G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors. Adv Second Messenger Phosphoprotein Res. 1997;31:263–277.

Published In

Adv Second Messenger Phosphoprotein Res

ISSN

1040-7952

Publication Date

1997

Volume

31

Start / End Page

263 / 277

Location

United States

Related Subject Headings

  • ras Proteins
  • Tyrosine
  • Signal Transduction
  • Receptors, Cell Surface
  • Phosphorylation
  • Phosphoproteins
  • Humans
  • GTP-Binding Proteins
  • Enzyme Activation
  • Calcium-Calmodulin-Dependent Protein Kinases