Controlling cytokine signaling by constitutive inhibitors

Kriti Rakesh, Devendra K. Agrawal

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)649-657
Number of pages9
JournalBiochemical Pharmacology
Volume70
Issue number5
DOIs
StatePublished - Sep 1 2005

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Protein Inhibitors of Activated STAT
Cytokines
Signal transduction
Ubiquitin
Phosphoric Monoester Hydrolases
Signal Transduction
Proteins
Suppressor of Cytokine Signaling Proteins
Janus Kinases
Phosphatases
Cell Surface Receptors
Transcription
Transducers
Genes
Research

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Controlling cytokine signaling by constitutive inhibitors. / Rakesh, Kriti; Agrawal, Devendra K.

In: Biochemical Pharmacology, Vol. 70, No. 5, 01.09.2005, p. 649-657.

Research output: Contribution to journalArticle

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