Involvement of Protein Kinase D1 in Signal Transduction from the Protein Kinase C Pathway to the Tyrosine Kinase Pathway in Response to Gonadotropin-releasing Hormone.

The Journal of Biological Chemistry
Sayomi Higa-NakamineHideyuki Yamamoto

Abstract

The receptor for gonadotropin-releasing hormone (GnRH) belongs to the G protein-coupled receptors (GPCRs), and its stimulation activates extracellular signal-regulated protein kinase (ERK). We found that the transactivation of ErbB4 was involved in GnRH-induced ERK activation in immortalized GnRH neurons (GT1-7 cells). We found also that GnRH induced the cleavage of ErbB4. In the present study, we examined signal transduction for the activation of ERK and the cleavage of ErbB4 after GnRH treatment. Both ERK activation and ErbB4 cleavage were completely inhibited by YM-254890, an inhibitor of Gq/11 proteins. Down-regulation of protein kinase C (PKC) markedly decreased both ERK activation and ErbB4 cleavage. Experiments with two types of PKC inhibitors, Gö 6976 and bisindolylmaleimide I, indicated that novel PKC isoforms but not conventional PKC isoforms were involved in ERK activation and ErbB4 cleavage. Our experiments indicated that the novel PKC isoforms activated protein kinase D (PKD) after GnRH treatment. Knockdown and inhibitor experiments suggested that PKD1 stimulated the phosphorylation of Pyk2 by constitutively activated Src and Fyn for ERK activation. Taken together, it is highly possible that PKD1 plays a critical r...Continue Reading

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Citations

Jan 18, 2016·The Journal of Allergy and Clinical Immunology·Avanti DesaiDean D Metcalfe
Nov 13, 2018·Journal of Cellular Physiology·Shiho Okitsu-SakurayamaHideyuki Yamamoto
Feb 13, 2019·The Journal of Biological Chemistry·Davide MalfaciniEvi Kostenis
Sep 29, 2020·Journal of Cellular Physiology·Shiho Okitsu-SakurayamaHideyuki Yamamoto

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