Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity.
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).
Tang
Pingtao
P
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cheng
Tammy P
TP
Agnello
Davide
D
Wu
Chang-You
CY
Hissong
Bruce D
BD
Watford
Wendy T
WT
Ahn
Hyun-Jong
HJ
Galon
Jerome
J
Moss
Joel
J
Vaughan
Martha
M
O'Shea
John J
JJ
Gadina
Massimo
M
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
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