TY - JOUR
T1 - Controlling cytokine signaling by constitutive inhibitors
AU - Rakesh, Kriti
AU - Agrawal, Devendra K.
PY - 2005/9/1
Y1 - 2005/9/1
N2 - Cytokines are secreted proteins that regulate diverse biological functions by binding to receptors at the cell surface to activate complex signal transduction pathways including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Stringent mechanisms of signal attenuation are essential for ensuring an appropriate, controlled cellular response. Three families of proteins, the SH2-containing phosphatases (SHP), the protein inhibitors of activated STATs (PIAS), and the suppressors of cytokine signaling (SOCS), inhibit specific and distinct aspects of cytokine signal transduction. The analysis of mice lacking genes for members of the SHP has shed much light on the roles of these proteins in vivo. In recent in vitro studies, the protein modifiers ubiquitin and small ubiquitin-like modifier (SUMO) have emerged as key players in the strategies employed by SOCS and PIAS to repress signaling. This review throws light on the mechanisms of action of these regulators as being evolved by the latest researches.
AB - Cytokines are secreted proteins that regulate diverse biological functions by binding to receptors at the cell surface to activate complex signal transduction pathways including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Stringent mechanisms of signal attenuation are essential for ensuring an appropriate, controlled cellular response. Three families of proteins, the SH2-containing phosphatases (SHP), the protein inhibitors of activated STATs (PIAS), and the suppressors of cytokine signaling (SOCS), inhibit specific and distinct aspects of cytokine signal transduction. The analysis of mice lacking genes for members of the SHP has shed much light on the roles of these proteins in vivo. In recent in vitro studies, the protein modifiers ubiquitin and small ubiquitin-like modifier (SUMO) have emerged as key players in the strategies employed by SOCS and PIAS to repress signaling. This review throws light on the mechanisms of action of these regulators as being evolved by the latest researches.
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U2 - 10.1016/j.bcp.2005.04.042
DO - 10.1016/j.bcp.2005.04.042
M3 - Article
C2 - 15936728
AN - SCOPUS:23044500093
VL - 70
SP - 649
EP - 657
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 5
ER -