title: Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity.
abstract: Cytokines regulate lymphocyte development and differentiation, but precisely how they control these processes is still poorly understood. By using microarray technology to detect cytokine-induced genes, we identified a cDNA encoding Cybr, which was increased markedly in cells incubated with IL-2 and IL-12. The mRNA was most abundant in hematopoietic cells and tissues. The predicted amino acid sequence is similar to that of GRP-1-associated protein (GRASP), a recently identified retinoic acid-induced cytohesin-binding protein. Physical interaction, dependent on the coiled-coil domains of Cybr and cytohesin-1, was demonstrated by coimmunoprecipitation of the overexpressed proteins from 293T cells. Cytohesin-1, in addition to its role in cell adhesion, is a guanine nucleotide-exchange protein activator of ARF GTPases. Acceleration of guanosine 5prime prime or minute-O-(thiotriphosphate) binding to ARF by cytohesin-1 in vitro was enhanced by Cybr. Because the binding protein modified activation of ADP ribosylation factor by cytohesin-1, we designate this cytokine-inducible protein Cybr (cytohesin binder and regulator).
authors.affiliation: Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Pingtao
authors.initials: P
authors.lastname: Tang
authors.forename: Tammy P
authors.initials: TP
authors.lastname: Cheng
authors.forename: Davide
authors.initials: D
authors.lastname: Agnello
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Wu
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hissong
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Jerome
authors.initials: J
authors.lastname: Galon
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.forename: Martha
authors.initials: M
authors.lastname: Vaughan
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Massimo
authors.initials: M
authors.lastname: Gadina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: C084539:CYTIP protein, human; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C513660:Cybr protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D007376:Interleukin-2; D008565:Membrane Proteins; D011506:Proteins; D014157:Transcription Factors; C100723:cytohesin-1; D018664:Interleukin-12