Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins
- Author(s)
- Hansen, JA; Lindberg, K; Hilton, DJ; Nielsen, JH; Billestrup, N;
- Details
- Publication Year 1999-11,Volume 13,Issue #11,Page 1832-1843
- Journal Title
- MOLECULAR ENDOCRINOLOGY
- Publication Type
- Journal Article
- Abstract
- In this study we have investigated the role of suppressor of cytokine signaling (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible SH2-containing protein (CIS) had no effect. By using chimeric SOCS proteins it was found that the ability of SOCS proteins to inhibit OH-mediated transcription was located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids C-terminal to the SH2 domain were required for the inhibitory activity, while a truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit GH-induced STAT5 (signal transducer and activator of transcription) activation. SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four SOCS proteins were able to bind to a tyrosine-phosphorylated glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the same 46 C-terminal amino acids for GH receptor binding as it did for inhibition of ON-mediated transcription and STAT5 activation, These data suggest that SOCS-1 and -3 can suppress ON-induced transcriptional activity, presumably by inhibiting the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.
- Publisher
- ENDOCRINE SOC
- Keywords
- STAT5 ACTIVATION; TYROSINE RESIDUES; IDENTIFICATION; FAMILY; CIS; PHOSPHORYLATION; SOCS-3; DOMAIN; CELLS
- Publisher's Version
- https://doi.org/10.1210/me.13.11.1832
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- Refer to copyright notice on published article.
Creation Date: 1999-11-01 12:00:00