Controlling cytokine signaling by constitutive inhibitors

Kriti Rakesh, Devendra K. Agrawal

    Research output: Contribution to journalArticlepeer-review

    99 Scopus citations


    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
    Issue number5
    StatePublished - Sep 1 2005

    All Science Journal Classification (ASJC) codes

    • Pharmacology


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