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Phospholipase Cgamma1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and

Jang Hyun Choi1, Hyeon Soo Kim, Sun-Hee Kim

  • 1National Research Laboratory of Signaling Network, Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Republic of Korea.

Nature Cell Biology
|November 28, 2006
PubMed

Insights

Phospholipase Cgamma1 (PLCgamma1) negatively regulates growth hormone signaling by interacting with Jak2. Its absence enhances growth hormone-induced proliferation and gene activation.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Endocrinology

Background:

  • Growth hormone (GH) regulates cellular functions via its receptor (GHR).
  • GH-mediated signaling pathways are understood, but regulatory mechanisms remain unclear.
  • Phospholipase Cgamma1 (PLCgamma1) is investigated for its role in GH signaling regulation.

Purpose of the Study:

  • To elucidate the role of PLCgamma1 in growth hormone signaling.
  • To investigate the interaction between PLCgamma1 and janus kinase 2 (Jak2).
  • To determine how PLCgamma1 modulates GH-induced cellular responses.

Main Methods:

  • Utilized PLCgamma1 knockout (PLCgamma1(-/-)) mouse embryonic fibroblasts (MEFs).
  • Assessed JAK2 and STAT5 phosphorylation via Western blotting.
  • Investigated protein-protein interactions using binding assays.
  • Examined c-Fos activation and cell proliferation.

Main Results:

  • PLCgamma1 deficiency significantly increased GH-induced JAK2 and STAT5 phosphorylation.
  • Re-expression or knockdown of PLCgamma1 modulated GH-induced Jak2 activation.
  • PLCgamma1 physically linked Jak2 and PTP-1B, influencing cytokine signaling.
  • GH-dependent c-Fos activation and proliferation were upregulated in PLCgamma1(-/-) MEFs.

Conclusions:

  • PLCgamma1 negatively regulates GH-mediated signaling by inhibiting Jak2 activation.
  • PLCgamma1 plays a critical role in controlling GH-induced cellular proliferation and gene expression.

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