Insulin induces suppressor of cytokine signaling-3 tyrosine phosphorylation through janus-activated kinase
- Author(s)
- Peraldi, P; Filloux, C; Emanuelli, B; Hilton, DJ; Van Obberghen, E;
- Details
- Publication Year 2001-07-06,Volume 276,Issue #27,Page 24614-24620
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Suppressor of cytokine signaling (SOCS) proteins were originally described as cytokine-induced molecules involved in negative feedback loops. We have shown that SOCS-3 is also a component of the insulin signaling network (1), Indeed, insulin leads to SOCS-3 expression in 3T3-L1 adipocytes. Once produced, SOCS-3 binds to phosphorylated tyrosine 960 of the insulin receptor and inhibits insulin signaling. Now we show that in 3T3-L1 adipocytes and in transfected COS-7 cells insulin leads to SOCS-3 tyrosine phosphorylation. This phosphorylation takes place on Tyr(204) and is dependent upon a functional SOCS-3 SH2 domain. Purified insulin receptor directly phosphorylates SOCS-3, However, in intact cells, a mutant of the insulin receptor, IRY960F, unable to bind SOCS-3, was as efficient as the wild type insulin receptor to phosphorylate SOCS-3, Importantly, IRY960F is as potent as the wild type insulin receptor to activate janus-activated kinase (Jak) 1 and Jak2, Furthermore, expression of a dominant negative form of Jak2 inhibits insulin-induced SOCS-3 tyrosine phosphorylation, ks transfected Jaks have been shown to cause SOCS-3 phosphorylation, we propose that insulin induces SOCS-3 phosphorylation through Jak activation. Our data indicate that SOCS-3 belongs to a class of tyrosine-phosphorylated insulin signaling molecules, the phosphorylation of which is not dependent upon a direct coupling with the insulin receptor but relies on the Jacks.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- PLECKSTRIN HOMOLOGY DOMAINS; MICE LACKING SUPPRESSOR; FACTOR-I RECEPTOR; SOCS-BOX MOTIF; STAT3 ACTIVATION; PROTEINS; BINDS; MECHANISMS; INHIBITION; SUBSTRATE
- Publisher's Version
- https://doi.org/10.1074/jbc.M102209200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-07-06 12:00:00