Phospholipase Cgamma1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B.
Growth hormone binds to its membrane receptor (GHR), whereby it regulates many cellular functions, including proliferation, differentiation and chemotaxis. However, although the activation of growth hormone-mediated signalling is well understood, the precise mechanism responsible for its regulation has not been elucidated. Here, we demonstrate that phospholipase Cgamma1 (PLCgamma1) modulates the action of growth hormone-mediated signalling by interacting with tyrosine kinase Jak2 (janus kinase 2) in a growth hormone-dependent manner. In the absence of PLCgamma1 (PLCgamma1(-/-)), growth hormone-induced JAK2 and STAT5 phosphorylation significantly increased in mouse embryonic fibroblasts (MEFs). Furthermore, the re-expression of PLCgamma1 reduced growth hormone-induced Jak2 activation. Growth hormone-induced Jak2 phosphorylation was enhanced by siRNA-specific knockdown of PLCgamma1. Interestingly, PLCgamma1 physically linked Jak2 and protein tyrosine phosphatase-1B (PTP-1B) by binding to both using different domains, and this process was implicated in the modulation of cytokine signalling through Jak2. In addition, in PLCgamma1(-/-) MEFs, growth hormone-dependent c-Fos activation was upregulated and growth hormone-induced proliferation was potentiated. These results suggest that PLCgamma1 has a key function in the regulation of growth hormone-mediated signalling by negatively regulating Jak2 activation.
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GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y
growth hormone PLCgamma1 growth hormone Jak2 growth hormone phospholipase Cgamma1 PLCgamma1 growth hormone tyrosine kinase Jak2 GHR tyrosine janus kinase 2 growth hormone PLCgamma1 PLCgamma1 growth hormone JAK2 STAT5 PLCgamma1 growth hormone Jak2 tyrosine Growth hormone Jak2 PLCgamma1 PLCgamma1 Jak2 protein tyrosine phosphatase-1B PTP-1B Phospholipase Cgamma1 Jak2 protein tyrosine phosphatase-1B tyrosine growth hormone Growth hormone cytokine Jak2 PLCgamma1 growth hormone c-Fos