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Proton-sensing GPCR-YAP Signalling Promotes Cell Proliferation and Survival.

ABSTRACT: The pHs of extracellular fluids (ECFs) in humans are consistently maintained at 7.35 to 7.45 in physiological conditions. Pathological changes, including infarction, tumourigenesis and inflammation, commonly result in decreases in the ECF pH in the affected tissues. In this study, we report that proliferation is promoted and apoptosis is inhibited by decreases in extracellular pH. Furthermore, we demonstrated that proton-sensing G-protein-coupled receptors (GPCRs) are required for the pH-dependent regulation of proliferation and apoptosis through the G protein ? subunit 12/13 (G12/13) and Rho GTPases. Next, we identified Yes-associated protein 1 (YAP) as a downstream effector of Rho signalling. Together, the results from our study demonstrate that extracellular pH can modulate cell proliferation and apoptosis by regulating the proton-sensing GPCR-YAP pathway.

SUBMITTER: Zhu H

PROVIDER: S-EPMC4551754 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Proton-sensing GPCR-YAP Signalling Promotes Cell Proliferation and Survival.

Zhu Hongyi H Cheng Xiangguo X Niu Xin X Zhang Yuelei Y Guan Junjie J Liu Xiaolin X Tao Shicong S Wang Yang Y Zhang Changqing C

International journal of biological sciences 20150808 10

The pHs of extracellular fluids (ECFs) in humans are consistently maintained at 7.35 to 7.45 in physiological conditions. Pathological changes, including infarction, tumourigenesis and inflammation, commonly result in decreases in the ECF pH in the affected tissues. In this study, we report that proliferation is promoted and apoptosis is inhibited by decreases in extracellular pH. Furthermore, we demonstrated that proton-sensing G-protein-coupled receptors (GPCRs) are required for the pH-depende ...[more]

PMID: 26327812

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