Letter abstract


Nature Cell Biology 8, 1389 - 1397 (2006)
Published online: 26 November 2006 | doi:10.1038/ncb1509

Phospholipase Cbig gamma1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B

Jang 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 Suh1

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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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  1. 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 to: Pann-Ghill Suh1 e-mail: pgs@postech.ac.kr



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