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Ras-dependent activation of MAP kinase pathway mediated by G-protein βγ subunits

Nature volume 369, pages 418–420 (1994)Cite this article

Abstract

MITOGEN-ACTIVATED protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors1,2. In turn, ERKs phosphorylate and regulate key intra-cellular enzymes and transcription factors involved in the control of cellular proliferation3,4. The tyrosine-kinase class of growth-factor receptors transmits signals to ERKs in a multistep process that involves Ras and a limited number of defined molecules5. In contrast, ERK activation by G-protein-coupled receptors is poorly understood3,6, as is the role of ras in this signalling pathway7,8. We have explored in COS-7 cells the mechanism of ERKs activation by ml and m2 muscarinic receptors, typical examples of receptors coupled through Gq proteins to induce phosphatidylinositol hydrolysis and to Gi proteins to inhibit adenylyl cyclase, respectively9. Here we present evidence that ERK activation is mediated by βγ subunits of heterotrimeric G proteins acting on a ras-dependent pathway.

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Affiliations

  1. Molecular Signalling Unit, Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Piero Crespo, Ningzhi Xu & J. Silvio Gutkind

  2. Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    William F. Simonds

Authors
  1. Piero Crespo
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  2. Ningzhi Xu
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  3. William F. Simonds
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  4. J. Silvio Gutkind
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Crespo, P., Xu, N., Simonds, W. et al. Ras-dependent activation of MAP kinase pathway mediated by G-protein βγ subunits. Nature 369, 418–420 (1994). https://doi.org/10.1038/369418a0

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