Regulation of interleukin-21 receptor expression and its signal transduction by WSB-2.
Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain (gammac) receptor subunit. We identified novel IL-21R-binding molecule, WD-40 repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal transduction. On the other hand, small interfering RNA for WSB-2 enhanced the expression level of IL-21R and IL-21-induced STAT3 activation, indicating that WSB-2 negatively controls the receptor expression. This report provides the first evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal transduction.
Nara
Hidetoshi
H
Department of Immunology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Onoda
Tadashi
T
Rahman
Mizanur
M
Araki
Akemi
A
Juliana
Farha M
FM
Tanaka
Nobuyuki
N
Asao
Hironobu
H
D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D053738:Interleukin-21 Receptor alpha Subunit / Q000096:biosynthesis*; D007378:Interleukins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins; D000098546:Interleukin-21
C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; C000656508:WSB2 protein, human; D000098546:Interleukin-21