CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling.

Published

Journal Article

CIS is a cytokine-induced SH2-containing protein that was originally cloned as an interleukin (IL)-3-inducible gene. CIS is known to associate with the IL-3 receptor beta chain and erythropoietin receptor and to inhibit signaling mediated by IL-3 and erythropoietin. We now demonstrate that CIS also interacts with the IL-2 receptor beta chain (IL-2Rbeta). This interaction requires the A region of IL-2Rbeta (residues 313-382), which also mediates the association of IL-2Rbeta with Lck and Jak3. Correspondingly, CIS inhibits functions associated with both of these kinases: Lck-mediated phosphorylation of IL-2Rbeta and IL-2-mediated activation of Stat5. Thus, we demonstrate that CIS can negatively control at least two independent IL-2 signaling pathways. Although a functional SH2 binding domain of CIS was not required for its interaction with IL-2Rbeta in vitro, its phosphotyrosine binding capability was essential for the inhibitory action of CIS. On this basis, we have generated a mutant form of CIS protein with an altered SH2 domain that acts as a dominant negative and should prove useful in further understanding CIS action.

Full Text

Duke Authors

Cited Authors

  • Aman, MJ; Migone, TS; Sasaki, A; Ascherman, DP; Zhu, MH; Soldaini, E; Imada, K; Miyajima, A; Yoshimura, A; Leonard, WJ

Published Date

  • October 15, 1999

Published In

Volume / Issue

  • 274 / 42

Start / End Page

  • 30266 - 30272

PubMed ID

  • 10514520

Pubmed Central ID

  • 10514520

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.274.42.30266

Language

  • eng

Conference Location

  • United States