Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro176 of human CISH protein.
The suppressor of cytokine signaling (SOCS) family members are negative regulators of cytokine signal transduction that inhibit the Jak/Stat pathway (1-3). The SOCS family consists of at least 8 members including the originally identified cytokine-inducible SH2-containing protein (CIS1), as well as SOCS1-7. Each SOCS family member contains a central SH2 domain and a conserved carboxy-terminal motif designated as the SOCS box. These proteins are important regulators of cytokine signaling, proliferation, differentiation, and immune responses.
CISH/CIS1, the first described member of the SOCS family, is induced by a number of cytokines including IL-2, IL-3, GM-CSF, and EPO (4). The CISH protein appears as a doublet around 32 and 37 kDa, the nature of which is unknown (4). CISH binds to phosphorylated cytokine receptors and can inhibit Stat5 activity (4-6). Expression of CISH is regulated by Stat5, thereby providing feedback modulation (5). Transgenic mice overexpressing CISH display phenotypes similar to Stat5 knockouts, including defects in mammary gland development and in T and NK cell regulation (6). Research studies have shown that polymorphisms within the CISH gene are associated with susceptibility to infectious diseases (7).
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