TY - JOUR
T1 - Activation of a CrkL-Stat5 signaling complex by type I interferons
AU - Fish, Eleanor N.
AU - Uddin, Shahab
AU - Korkmaz, Mete
AU - Majchrzak, Beata
AU - Druker, Brian J.
AU - Platanias, Leonidas C.
PY - 1999/1/8
Y1 - 1999/1/8
N2 - Type I interferons (IFNα and IFNβ) transduce signals by inducing tyrosine phosphorylation of Jaks and Stats, as well as the CrkL adapter, an SH2/SH3-containing protein which provides a link to downstream pathways that mediate growth inhibition. We report that Stat5 interacts constitutively with the IFN receptor-associated Tyk-2 kinase, and during IFNα stimulation its tyrosine-phosphorylated form acts as a docking site for the SH2 domain of CrkL. CrkL and Stat5 then form a complex that translocates to the nucleus. This IFN-inducible CrkL-Stat5 complex binds in vitro to the TTCTAGGAA palindromic element found in the promoters of a subset of IFN-stimulated genes. Thus, during activation of the Type I IFN receptor, CrkL functions as a nuclear adapter protein and, in association with Stat5, regulates gene transcription through DNA binding.
AB - Type I interferons (IFNα and IFNβ) transduce signals by inducing tyrosine phosphorylation of Jaks and Stats, as well as the CrkL adapter, an SH2/SH3-containing protein which provides a link to downstream pathways that mediate growth inhibition. We report that Stat5 interacts constitutively with the IFN receptor-associated Tyk-2 kinase, and during IFNα stimulation its tyrosine-phosphorylated form acts as a docking site for the SH2 domain of CrkL. CrkL and Stat5 then form a complex that translocates to the nucleus. This IFN-inducible CrkL-Stat5 complex binds in vitro to the TTCTAGGAA palindromic element found in the promoters of a subset of IFN-stimulated genes. Thus, during activation of the Type I IFN receptor, CrkL functions as a nuclear adapter protein and, in association with Stat5, regulates gene transcription through DNA binding.
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U2 - 10.1074/jbc.274.2.571
DO - 10.1074/jbc.274.2.571
M3 - Article
C2 - 9872990
AN - SCOPUS:0033534450
SN - 0021-9258
VL - 274
SP - 571
EP - 573
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 2
ER -