Title : Role of the cytokine-inducible SH2 protein CIS in desensitization of STAT5b signaling by continuous growth hormone.

Pub. Date : 2000 Dec 15

PMID : 10991939






3 Functional Relationships(s)
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1 Growth hormone (GH)-inducible suppressors of cytokine signaling (SOCS/CIS proteins) inhibit GH receptor (GHR) signaling to STAT5b via phosphotyrosine-dependent binding interactions with the tyrosine kinase JAK2 (SOCS-1) and/or the cytoplasmic tail of GHR (CIS and SOCS-3). Phosphotyrosine Janus kinase 2 Rattus norvegicus
2 CIS is shown to inhibit GHR-JAK2 signaling by two distinct mechanisms: by a partial inhibition that is decreased at elevated STAT5b levels and may involve competition between CIS and STAT5b for common GHR cytoplasmic tail phosphotyrosine-binding sites; and by a time-dependent inhibition, not seen with SOCS-1 or SOCS-3, that involves proteasome action. Phosphotyrosine Janus kinase 2 Rattus norvegicus
3 Finally, the down-regulation of GHR-JAK2 signaling to STAT5b seen in continuous GH-treated cells could be prevented by treatment of cells with the proteasome inhibitor MG132 or by expression of CIS-R107K, a selective, dominant-negative inhibitor of CIS activity. benzyloxycarbonylleucyl-leucyl-leucine aldehyde Janus kinase 2 Rattus norvegicus