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Publication : A conserved IFN-alpha receptor tyrosine motif directs the biological response to type I IFNs.

First Author  Zhao W Year  2008
Journal  J Immunol Volume  180
Issue  8 Pages  5483-9
PubMed ID  18390731 Mgi Jnum  J:134253
Mgi Id  MGI:3785194 Doi  10.4049/jimmunol.180.8.5483
Citation  Zhao W, et al. (2008) A conserved IFN-alpha receptor tyrosine motif directs the biological response to type I IFNs. J Immunol 180(8):5483-9
abstractText  Mammalian type I IFNs (IFN-Is) mediate their potent biological activities through an evolutionarily conserved IFN-alpha receptor (IFNAR), consisting of IFNAR1 and IFNAR2. These two chains direct the rapid activation of two founding members of the STAT family of transcription factors, STAT1 and STAT2. To understand how IFN-Is direct the recruitment and activation of STATs, a series of mutant murine IFNAR1 and IFNAR2 receptors were generated and evaluated in IFNAR1 and IFNAR2 knockout cells. These studies reveal that a single conserved IFNAR2 tyrosine, Y(510), plays a critical role in directing the IFN-I-dependent activation of STAT1 and STAT2, both in murine fibroblasts and macrophages. A second IFNAR2 tyrosine, Y(335), plays a more minor role. Likewise, Y(510) > Y(335) play a critical role in the induction of genes and antiviral activity traditionally associated with IFN-Is.
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