Nature Cell Biology
- 8, 1389 - 1397 (2006)
Published online: 26 November 2006; | doi:10.1038/ncb1509
Phospholipase C 1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1BJang Hyun Choi1, Hyeon Soo Kim1, Sun-Hee Kim1, Yong Ryoul Yang1, Yun Soo Bae2, Jong-Soo Chang3, H. Moo Kwon4, Sung Ho Ryu1 & Pann-Ghill Suh11
National Research Laboratory of Signaling Network,Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Republic of Korea. 2
Divisions of Molecular Life Sciences, Center for Cell Signalling Research, Ewha Womans University, Seoul 120-750, Republic of Korea. 3
Department of Life Science, College of Natural Science, Daejin University, Kyeonggido 487-711, Republic of Korea. 4
Divisions of Nephrology, University of Maryland, Baltimore, MD 21201, USA.
Correspondence should be addressed to Pann-Ghill Suh pgs@postech.ac.kr 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 C 1 (PLC1) 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 PLC1 (PLC1-/-), growth hormone-induced JAK2 and STAT5 phosphorylation significantly increased in mouse embryonic fibroblasts (MEFs). Furthermore, the re-expression of PLC1 reduced growth hormone-induced Jak2 activation. Growth hormone-induced Jak2 phosphorylation was enhanced by siRNA-specific knockdown of PLC1. Interestingly, PLC1 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 PLC1-/- MEFs, growth hormone-dependent c-Fos activation was upregulated and growth hormone-induced proliferation was potentiated. These results suggest that PLC1 has a key function in the regulation of growth hormone-mediated signalling by negatively regulating Jak2 activation.
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