SOCS2 regulation of growth hormone signaling requires a canonical interaction with phosphotyrosine
- Author(s)
- Li, K; Guzman, LM; Whitehead, L; Leong, E; Kueh, A; Alexander, WS; Kershaw, NJ; Babon, JJ; Doggett, K; Nicholson, SE;
- Journal Title
- Bioscience Reports
- Publication Type
- epub ahead of print
- Abstract
- Suppressor Of Cytokine Signaling (SOCS) 2 is the critical negative regulator of growth hormone (GH) and prolactin signaling. Mice lacking SOCS2 display gigantism with increased body weight and length, and an enhanced response to GH treatment. Here we characterized mice carrying a germ-line R96C mutation within the SOCS2-SH2 domain, which disrupts the ability of SOCS2 to interact with tyrosine phosphorylated targets. Socs2R96C/R96C mice displayed a similar increase in growth as previously observed in SOCS2 null (Socs2-/-) mice, with a proportional increase in body and organ weight, and bone length. Embryonic fibroblasts isolated from Socs2R96C/R96C and Socs2-/- mice also showed a comparable increase in phosphorylation of STAT5 following GH stimulation, indicating the critical role of phosphotyrosine binding in SOCS2 function.
- Publisher
- Portland Press
- Keywords
- SH2 domain; Socs2; growth hormone; phosphotyrosine
- Research Division(s)
- Inflammation; Advanced Technology And Biology; Blood Cells And Blood Cancer; Structural Biology
- PubMed ID
- 36398696
- Publisher's Version
- https://doi.org/10.1042/bsr20221683
- Open Access at Publisher's Site
https://doi.org/10.1042/BSR20221683- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-12-13 03:12:54
Last Modified: 2022-12-14 11:41:18