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Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway.

Publication ,  Journal Article
van Biesen, T; Hawes, BE; Luttrell, DK; Krueger, KM; Touhara, K; Porfiri, E; Sakaue, M; Luttrell, LM; Lefkowitz, RJ
Published in: Nature
August 31, 1995

Mitogen-activated protein (MAP) kinases mediate the phosphorylation and activation of nuclear transcription factors that regulate cell growth. MAP kinase activation may result from stimulation of either tyrosine-kinase (RTK) receptors, which possess intrinsic tyrosine kinase activity, or G-protein-coupled receptors (GPCR). RTK-mediated mitogenic signalling involves a series of SH2- and SH3-dependent protein-protein interactions between tyrosine-phosphorylated receptor, Shc, Grb2 and Sos, resulting in Ras-dependent MAP kinase activation. The beta gamma subunits of heterotrimeric G proteins (G beta gamma) also mediate Ras-dependent MAP kinase activation by an as-yet unknown mechanism. Here we demonstrate that activation of MAP kinase by Gi-coupled receptors is preceded by the G beta gamma-mediated tyrosine phosphorylation of Shc, leading to an increased functional association between Shc, Grb2 and Sos. Moreover, disruption of the Shc-Grb2-Sos complex blocks G beta gamma-mediated MAP kinase activation, indicating that G beta gamma does not mediate MAP kinase activation by a direct interaction with Sos. These results indicate that G beta gamma-mediated MAP kinase activation is initiated by a tyrosine phosphorylation event and proceeds by a pathway common to both GPCRs and RTKs.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

August 31, 1995

Volume

376

Issue

6543

Start / End Page

781 / 784

Location

England

Related Subject Headings

  • Tyrosine
  • Son of Sevenless Proteins
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Recombinant Proteins
  • Receptor Protein-Tyrosine Kinases
  • Proteins
  • Protein Kinases
  • Phosphorylation
  • Membrane Proteins
 

Citation

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van Biesen, T., Hawes, B. E., Luttrell, D. K., Krueger, K. M., Touhara, K., Porfiri, E., … Lefkowitz, R. J. (1995). Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature, 376(6543), 781–784. https://doi.org/10.1038/376781a0
Biesen, T. van, B. E. Hawes, D. K. Luttrell, K. M. Krueger, K. Touhara, E. Porfiri, M. Sakaue, L. M. Luttrell, and R. J. Lefkowitz. “Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway.Nature 376, no. 6543 (August 31, 1995): 781–84. https://doi.org/10.1038/376781a0.
van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, et al. Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature. 1995 Aug 31;376(6543):781–4.
van Biesen, T., et al. “Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway.Nature, vol. 376, no. 6543, Aug. 1995, pp. 781–84. Pubmed, doi:10.1038/376781a0.
van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, Sakaue M, Luttrell LM, Lefkowitz RJ. Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature. 1995 Aug 31;376(6543):781–784.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

August 31, 1995

Volume

376

Issue

6543

Start / End Page

781 / 784

Location

England

Related Subject Headings

  • Tyrosine
  • Son of Sevenless Proteins
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Recombinant Proteins
  • Receptor Protein-Tyrosine Kinases
  • Proteins
  • Protein Kinases
  • Phosphorylation
  • Membrane Proteins