TY - JOUR
T1 - The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein
AU - Ahmad, Sarfraz
AU - Alsayed, Yazan M.
AU - Druker, Brian J.
AU - Platanias, Leonidas C.
PY - 1997/11/28
Y1 - 1997/11/28
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.272.48.29991
DO - 10.1074/jbc.272.48.29991
M3 - Article
C2 - 9374471
AN - SCOPUS:0030778425
SN - 0021-9258
VL - 272
SP - 29991
EP - 29994
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -