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Phospholipase C‐γ1 negatively regulates growth hormone signaling by forming a ternary complex with Jak2 and protein tyrosine phosphatase‐1B
Author(s) -
Choi Jang Hyun,
Kim Sun Hee,
Ryu Sung Ho,
Suh PannGhill
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb8
Subject(s) - protein tyrosine phosphatase , tyrosine phosphorylation , microbiology and biotechnology , phosphorylation , signal transduction , janus kinase 2 , growth hormone receptor , phospholipase c , stat5 , chemistry , phosphatase , biology , medicine , biochemistry , hormone , growth hormone
Growth hormone (GH) binds to its membrane receptor (GHR), whereby it regulates many cellular functions like proliferation, differentiation and chemotaxis. However, although the activation of GH‐mediated signaling is well understood, the precise mechanism responsible for its regulation has not been elucidated. In this study, we demonstrate that PLC‐γ1 modulates the action of GH‐mediated signaling by interacting with tyrosine kinase Jak2 in a GH‐dependent manner. In the absence of PLC‐γ1 (PLC‐γ1 −/− MEFs), GH‐induced JAK2 and STAT5 phosphorylations significantly increased, furthermore the re‐expression of PLC‐γ1 reduced GH‐induced Jak2 activation. Moreover, GH‐induced JAK2 phosphorylation was enhanced by siRNA specific knock‐down of PLC‐γ1. Interestingly, PLC‐γ1 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 signaling via Jak2. In addition, in PLC‐γ1 −/− MEFs, GH‐dependent c‐Fos activation was up‐regulated, and GH‐induced proliferation was potentiated. These results suggest that PLC‐γ1 plays a key role in the regulation of GH‐mediated signaling by negatively regulating Jak2 activation.