Redox Regulation of Interleukin-4 Signaling

Pankaj Sharma, Rikhia Chakraborty, Lu Wang, Booki Min, Michel L. Tremblay, Tsukasa Kawahara, J. David Lambeth, S. Jaharul Haque*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The physiologic control of cytokine receptor activation is primarily mediated by reciprocal activation of receptor-associated protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Here, we show that immediately after ligand-dependent activation, interleukin (IL)-4 receptor generated reactive oxygen species (ROS) via phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase (NOX)1 and NOX5L. ROS, in turn, promoted IL-4 receptor activation by oxidatively inactivating PTP1B that physically associated with and deactivated IL-4 receptor. However, ROS were not required for the initiation of IL-4 receptor activation. ROS generated by other cytokine receptors, including those for erythropoietin, tumor necrosis factor-α, or IL-3, also promoted IL-4 signaling. These data indicate that inactivation of receptor-associated PTP activity by cytokine-generated ROS is a physiologic mechanism for the amplification of cytokine receptor activation in both cis and trans, revealing a role for ROS in cytokine crosstalk.

Original languageEnglish (US)
Pages (from-to)551-564
Number of pages14
Issue number4
StatePublished - Oct 17 2008
Externally publishedYes



ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology


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