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Published online before print December 23, 2003

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1003507

Received for publication October 28, 2003.

Accepted for publication October 29, 2003.

Article

SOCS suppressors, regulators, and degraders

Department of Microbiology and Immunology, Queen’s University, Belfast, Northern Ireland

^@ To whom correspondence should be addressed. E-mail: jim.johnston{at}qub.ac.uk.

	Abstract

Suppressors of cytokine signaling proteins have been identified as inhibitors of cytokine signaling and have been shown to act in a classical feedback loop. The prototype members of this family, cytokine-inducible Src homology 2-containing protein and suppressor of cytokine signaling (SOCS)1, were cloned as cytokine-inducible immediate early genes that could inhibit the activation of signal transducer and activator of transcription factors and block biological responses to several cytokines. Although steady progress has been made in the identification of SOCS and their physiological importance, it has not yet been discovered precisely how SOCS proteins function. Many recent findings indicate that the SOCS act as adaptors that regulate the turnover of certain substrates by interacting with and activating an E3 ubiquitin ligase. Here, I explore recent evidence (presented at the International Cytokine Society meeting in Dublin, Ireland, September 2003) that SOCS molecules may not act simply as regulators of cytokine responses but may also play an essential role in determining cell fate and controlling cell differentiation.

Key Words: STAT • CIS • growth hormone

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