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Involvement of protein tyrosine phosphatases in activation of the trimeric G protein Gq/11

Oncogene volume 18, pages 7399–7402 (1999)Cite this article

Abstract

A variety of receptors coupled to the heterotrimeric guanine nucleotide-binding protein Gq/11 stimulate intracellular Ca2+ release through inositol (1,4,5)-trisphos-phate (IP3) formation. We previously reported that tyrosine phosphorylation of the α subunit of the Gq/11 protein by protein tyrosine kinases (PTKs) regulates the activation of Gq/11 protein. Here we show that protein tyrosine phosphatases (PTPs) are also essential for Gq/11 protein activation. We find that Gq/11 protein-coupled receptor-mediated formation of IP3 is blocked by PTP inhibitors as well as PTK inhibitors. These inhibitors act prior to Gq/11 protein activation. Tyrosine phosphorylation of the α subunit of Gq/11 appears to inhibit its interaction with receptors. Thus, PTP is required for controlling the level of tyrosine phosphorylation of the α subunit of Gq/11 to promote its interaction with receptors. Therefore, we conclude that PTKs and PTPs co-operate to proceed activation cycle of the Gq/11 protein through tyrosine phosphorylation and de-phosphorylation of the α subunit of Gq/11.

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Acknowledgements

We thank N Sekiyama for assistance with measuring IP3 formation, Y Bessho for assistance with Ca2+ imaging, K Haga, T Haga, K Kimura and H Itoh for valuable discussion. This work is supported by a grant for Advanced Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Hisashi Umemori, Takashi Hayashi & Tadashi Yamamoto

  2. Department of Molecular Neurobiology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Takafumi Inoue & Katsuhiko Mikoshiba

  3. Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto, 606-8501, Japan

    Shigetada Nakanishi

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  1. Hisashi Umemori
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Umemori, H., Hayashi, T., Inoue, T. et al. Involvement of protein tyrosine phosphatases in activation of the trimeric G protein Gq/11. Oncogene 18, 7399–7402 (1999). https://doi.org/10.1038/sj.onc.1203152

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