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Phospholipase Cγ1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B
- Phospholipase Cγ1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B
- Choi J.H.; Kim H.S.; Kim S.-H.; Yang Y.R.; Bae Y.S.; Chang J.-S.; Moo Kwon H.; Ryu S.H.; Suh P.-G.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Nature Cell Biology
- vol. 8, no. 12, pp. 1389 - 1397
- SCI; SCIE; SCOPUS
- 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.
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