Phospholipase C gamma 1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B
SCIE
SCOPUS
- Title
- Phospholipase C gamma 1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B
- Authors
- Choi, JH; Kim, HS; Kim, SH; Yang, YR; Bae, YS; Chang, JS; Kwon, HM; Ryu, SH; Suh, PG
- Date Issued
- 2006-12
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- 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 gamma 1 (PLC gamma 1) 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 PLC gamma 1 (PLC gamma 1(-/-)), growth hormone-induced JAK2 and STAT5 phosphorylation significantly increased in mouse embryonic fibroblasts (MEFs). Furthermore, the re-expression of PLC gamma 1 reduced growth hormone-induced Jak2 activation. Growth hormone-induced Jak2 phosphorylation was enhanced by siRNA-specific knockdown of PLC gamma 1. Interestingly, PLC gamma 1 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 PLC gamma 1(-/-) MEFs, growth hormone-dependent c-Fos activation was upregulated and growth hormone-induced proliferation was potentiated. These results suggest that PLC gamma 1 has a key function in the regulation of growth hormone-mediated signalling by negatively regulating Jak2 activation.
- Keywords
- NUCLEOTIDE EXCHANGE FACTOR; FACTOR-RECEPTOR; INSULIN SENSITIVITY; C-FOS; MICE; 1B; KINASE; ENDOCYTOSIS; ACTIVATION; FAILURE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/23700
- DOI
- 10.1038/NCB1509
- ISSN
- 1465-7392
- Article Type
- Article
- Citation
- NATURE CELL BIOLOGY, vol. 8, no. 12, page. 1389 - U53, 2006-12
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.