Interaction of stress-activated protein kinase-interacting protein-1 with the interferon receptor subunit IFNAR2 in uterine endometrium.
During early pregnancy in ruminants, a type I interferon (IFN-tau) signals from the conceptus to the mother to ensure the functional survival of the corpus luteum. IFN-tau operates through binding to the type I IFN receptor (IFNR). Here we have explored the possibility that IFNAR2, one of the two subunits of the receptor, might interact with hitherto unknown signal transduction factors in the uterus that link IFN action to pathways other than the well established Janus kinase-signal transducer and activator of transcription pathways. A yeast two-hybrid screen of an ovine (ov) endometrial cDNA library with the carboxyl-terminal 185 amino acids of ovIFNAR2 as bait identified stress-activated protein kinase-interacting protein 1 (ovSin1) as a protein that bound constitutively through its own carboxyl terminus to the receptor. ovSin1 is a little studied, 522-amino acid-long polypeptide (molecular weight, 59,200) that is highly conserved across vertebrates, but has identifiable orthologs in Drosophila and yeast. It appears to be expressed ubiquitously in mammals, although in low abundance, in a wide range of mammalian tissues in addition to endometrium. Sin1 mRNA occurs in at least two alternatively spliced forms, the smaller of which lacks a 108-bp internal exon. ovSin1, although not exhibiting features of a membrane-spanning protein, such as IFNAR2, is concentrated predominantly in luminal and glandular epithelial cells of the uterine endometrium. When ovSin1 and ovIFNAR2 are coexpressed, the two proteins can be coimmunoprecipitated and colocalized to the plasma membrane and to perinuclear structures. Sin1 provides a possible link among type I IFN action, stress-activated signaling pathways, and control of prostaglandin production.
Wang
Shu-Zong
SZ
Department of Veterinary Pathology, University of Missouri, Columbia, Missouri 65211, USA.
Roberts
R Michael
RM
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D047468:Immunoprecipitation; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism*; D012756:Sheep; D014162:Transfection; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics
D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta