Phospholipase Cγ1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B

Jang Hyun Choi, Hyeon Soo Kim, Sun Hee Kim, Yong Ryoul Yang, Yun Soo Bae, Jong Soo Chang, H. Moo Kwon, Sung Ho Ryu, Pann Ghill Suh

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 Cγ1 (PLCγ1) 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 PLCγ1 (PLCγ1-/-), growth hormone-induced JAK2 and STAT5 phosphorylation significantly increased in mouse embryonic fibroblasts (MEFs). Furthermore, the re-expression of PLCγ1 reduced growth hormone-induced Jak2 activation. Growth hormone-induced Jak2 phosphorylation was enhanced by siRNA-specific knockdown of PLCγ1. Interestingly, PLCγ1 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 PLCγ1-/- MEFs, growth hormone-dependent c-Fos activation was upregulated and growth hormone-induced proliferation was potentiated. These results suggest that PLCγ1 has a key function in the regulation of growth hormone-mediated signalling by negatively regulating Jak2 activation.

Original languageEnglish
Pages (from-to)1389-1397
Number of pages9
JournalNature Cell Biology
Volume8
Issue number12
DOIs
Publication statusPublished - 2006 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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