Interaction of IL-2Rβ and γc chains with Jak1 and Jak3: Implications for XSCID and XCID

Sarah M. Russell, James A. Johnston, Masayuki Noguchi, Masaru Kawamura, Chris M. Bacon, Michael Friedmann, Maria Berg, Daniel W. McVicar, Bruce A. Witthuhn, Olli Silvennoinen, Armond S. Goldman, Frank C. Schmalstieg, James N. Ihle, John J. O'Shea, Warren J. Leonard

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561 Scopus citations

Abstract

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor β (IL-2Rβ) and common γ (γc) chains. Mutations of γc can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain γc), and IL-9 (whose receptor is shown here to contain γc) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2Rβ and γc, respectively; IL-2 induced Jak3-IL-2Rβ and increased Jak3-γc associations. Truncations of γc, and a γc, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased γC-Jak3 association. Thus, γc mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Original languageEnglish (US)
Pages (from-to)1042-1045
Number of pages4
JournalScience
Volume266
Issue number5187
DOIs
StatePublished - 1994

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