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J Biol Chem. 1997 Nov 28;272(48):29991-4.

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

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  • 1Section of Hematology-Oncology, University of Illinois at Chicago and West Side Veterans Administration Hospital, Chicago, Illinois 60607, USA.

Abstract

Interferon (IFN) alpha 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 IFNalpha-dependent association of CrkL with Tyk-2 in intact cells. Two other Type I IFNs, IFNbeta and IFNomega, also induce tyrosine phosphorylation of CrkL, suggesting that the protein is involved in the signaling pathways of several different Type I IFNs. In the IFNalpha-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.

PMID:
9374471
[PubMed - indexed for MEDLINE]
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