Regulation of interleukin-21 Receptor Expression and Its Signal Transduction by WSB-2

Biochem Biophys Res Commun. 2010 Feb 5;392(2):171-7. doi: 10.1016/j.bbrc.2010.01.004. Epub 2010 Jan 6.

Abstract

Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain (gammac) receptor subunit. We identified novel IL-21R-binding molecule, WD-40 repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal transduction. On the other hand, small interfering RNA for WSB-2 enhanced the expression level of IL-21R and IL-21-induced STAT3 activation, indicating that WSB-2 negatively controls the receptor expression. This report provides the first evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Immunoprecipitation
  • Interleukin-21 Receptor alpha Subunit / biosynthesis*
  • Interleukins / metabolism*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • IL21R protein, human
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Wsb-2 protein, human
  • interleukin-21