The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein

Sarfraz Ahmad, Yazan M. Alsayed, Brian J. Druker, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Interferon (IFN) α induces rapid and transient tyrosine phosphorylation of the Src homology 2/Src homology 3 (SH2/SH3)-containing CrkL adaptor protein in a time- and dose-dependent manner. Such phosphorylation is most likely regulated by the Type I interferon receptor (IFNR)-associated Tyk-2 kinase, as suggested by the detection of Type I IFN-dependent tyrosine kinase activity in anti-CrkL immunoprecipitates and the IFNα-dependent association of CrkL with Tyk-2 in intact cells. Two other Type I IFNs, IFNβ and IFNω, also induce tyrosine phosphorylation of CrkL, suggesting that the protein is involved in the signaling pathways of several different Type I IFNs. In the IFNα-sensitive U-266 and Daudi cell lines, CrkL interacts via its N terminus SH3 domain with the guanine exchange factor C3G that regulates activation of Rap-1, a small G-protein that exhibits tumor suppressor activity. Thus, tyrosine phosphorylation of CrkL links the functional Type I IFNR complex to the C3G-Rap-1 signaling cascade that mediates growth inhibitory responses.

Original languageEnglish (US)
Pages (from-to)29991-29994
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number48
DOIs
StatePublished - Nov 28 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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