Am J Clin Exp Immunol 2013;2(1):1-29

Review Article
SOCS proteins in development and disease

Monique C Trengove, Alister C Ward

School of Medicine and Strategic Research Centre in Molecular & Medical Research, Deakin University, Geelong,
Victoria, Australia

Received December 27, 2012; Accepted January 22, 2013; Epub February 27, 2013; Published March 9, 2013

Abstract: Cytokine and growth factor signaling mediates essential roles in the differentiation, proliferation, survival and
function of a number of cell lineages. This is achieved via specific receptors located on the surface of target cells, with
ligand binding activating key intracellular signal transduction cascades to mediate the requisite cellular outcome.
Effective resolution of receptor signaling is also essential, with excessive signaling having the potential for pathological
consequences. The Suppressor of cytokine signaling (SOCS) family of proteins represent one important mechanism to
extinguish cytokine and growth factor receptor signaling. There are 8 SOCS proteins in mammals; SOCS1-7 and the
alternatively named Cytokine-inducible SH2-containing protein (CISH). SOCS1-3 and CISH are predominantly
associated with the regulation of cytokine receptor signaling, while SOCS4-7 are more commonly involved in the control
of Receptor tyrosine kinase (RTK) signaling. Individual SOCS proteins are typically induced by specific cytokines and
growth factors, thereby generating a negative feedback loop. As a consequence of their regulatory properties, SOCS
proteins have important functions in development and homeostasis, with increasing recognition of their role in disease,
particularly their tumor suppressor and anti-inflammatory functions. This review provides a synthesis of our current
understanding of the SOCS family, with an emphasis on their immune and hematopoietic roles. (AJCEI1212006).

Keywords: SOCS, development, immunity, disease, JAK-STAT, cytokine, growth factor, signalling, receptor tyrosine

Address correspondence to: Dr. Alister C Ward, School of Medicine, Deakin University, Pigdons Road, Geelong Victoria
3217, Australia. Phone: +61-3 5227 2041; Fax: +61-3 5227 2945; E-mail:
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