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

M. Javad Aman, Thi Sau Migone, Atsuo Sasaki, Dana P. Ascherman, Ming Hua Zhu, Elisabetta Soldaini, Kazunori Imada, Atsushi Miyajima, Akihiko Yoshimura, Warren J. Leonard

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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 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 β chain (IL-2Rβ). This interaction requires the A region of IL-2Rβ (residues 313-382), which also mediates the association of IL-2Rβ with Lck and Jak3. Correspondingly, CIS inhibits functions associated with both of these kinases: Lck-mediated phosphorylation of IL-2Rβ 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-2Rβ 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.

Original languageEnglish
Pages (from-to)30266-30272
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number42
DOIs
Publication statusPublished - 1999 Oct 15
Externally publishedYes

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Interleukin-2 Receptors
Interleukins
Interleukin-2
src Homology Domains
Interleukin-3
Interleukin-3 Receptors
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Erythropoietin Receptors
Phosphotyrosine
Phosphorylation
Erythropoietin
Proteins
Genes
Chemical activation
Association reactions
Cytokines

ASJC Scopus subject areas

  • Biochemistry

Cite this

Aman, M. J., Migone, T. S., Sasaki, A., Ascherman, D. P., Zhu, M. H., Soldaini, E., ... Leonard, W. J. (1999). CIS associates with the interleukin-2 receptor β chain and inhibits interleukin-2-dependent signaling. Journal of Biological Chemistry, 274(42), 30266-30272. https://doi.org/10.1074/jbc.274.42.30266

CIS associates with the interleukin-2 receptor β chain and inhibits interleukin-2-dependent signaling. / Aman, M. Javad; Migone, Thi Sau; Sasaki, Atsuo; Ascherman, Dana P.; Zhu, Ming Hua; Soldaini, Elisabetta; Imada, Kazunori; Miyajima, Atsushi; Yoshimura, Akihiko; Leonard, Warren J.

In: Journal of Biological Chemistry, Vol. 274, No. 42, 15.10.1999, p. 30266-30272.

Research output: Contribution to journalArticle

Aman, MJ, Migone, TS, Sasaki, A, Ascherman, DP, Zhu, MH, Soldaini, E, Imada, K, Miyajima, A, Yoshimura, A & Leonard, WJ 1999, 'CIS associates with the interleukin-2 receptor β chain and inhibits interleukin-2-dependent signaling', Journal of Biological Chemistry, vol. 274, no. 42, pp. 30266-30272. https://doi.org/10.1074/jbc.274.42.30266
Aman, M. Javad ; Migone, Thi Sau ; Sasaki, Atsuo ; Ascherman, Dana P. ; Zhu, Ming Hua ; Soldaini, Elisabetta ; Imada, Kazunori ; Miyajima, Atsushi ; Yoshimura, Akihiko ; Leonard, Warren J. / CIS associates with the interleukin-2 receptor β chain and inhibits interleukin-2-dependent signaling. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 42. pp. 30266-30272.
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AU - Leonard, Warren J.

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