Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 11
Phospholipase C-g1 attenuates growth hormone signaling by forming a ternary complex
with Jak2 and protein tyrosine phosphatase-1B
Jang Hyun Choi1, Hyeon Soo Kim1, Sun-Hee Kim1, Yun Soo Bae2, H. Moo Kwon3,
Sung Ho Ryu1, and Pann-Ghill Suh1*
1 Department of Life Science, Pohang University of Science and Technology, Pohang,
Kyungbuk, 790-784, Republic of Korea, E-mail : pgs@postech.ac.kr
2 Divisions of Molecular Life Sciences, Center for Cell Signaling Research, Ewha
Womans University, Seoul 120-750, Republic of Korea
3 Divisions of Nephrology, University of Maryland, Baltimore, Maryland 21201, USA
Growth hormone (GH) binds to its membrane receptor (GHR) and regulates many cellular
functions such as proliferation, differentiation and chemotaxis. While the activation of GHmediated
signaling is well understood, the precise mechanism responsible for its regulation
has not been well assessed. In this study, we demonstrate that PLC-$1 modulates the action of
GH-mediated signaling by interacting with tyrosine kinase Jak2 in a GH-dependent manner.
In the absence of PLC-$1 (PLC-$1-/- MEFs), GH-induced JAK2 and STAT5
phosphorylations significantly increased and the re-expression of PLC-$1 reduced GHinduced
Jak2 activation. Furthermore, GH-induced JAK2 phosphorylation was enhanced by
the specific knock-down of PLC-$1 using siRNA. Interestingly, PLC-$1 physically linked
Jak2 with protein tyrosine phosphatase-1B (PTP-1B), which was implicated in the modulation
of cytokine signaling via Jak2. In PLC-$1-/- MEFs, GH-dependent activation of both STAT-5
and c-Fos were up-regulated, and GH-induced proliferation was potentiated. These results
suggest that PLC-$1 plays a key role in regulation of GH-mediated signaling by attenuating
the activation of JAK2.
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