title: Identification and functional analysis of CBLB mutations in type 1 diabetes.
abstract: Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity. In particular, a nonsense mutation in Cblb has been identified in a rat model of autoimmune type 1 diabetes. To clarify the possible involvement of CBLB mutation in type 1 diabetes in humans, we performed mutation screening of CBLB and characterized functional properties of the mutations in Japanese subjects. Six missense mutations (A155V, F328L, N466D, K837R, T882A, and R968L) were identified in one diabetic subject each, excepting N466D. Of these mutations, F328L showed impaired suppression of T-cell activation and was a loss-of-function mutation. These data suggest that the F328L mutation is involved in the development of autoimmune diseases including type 1 diabetes, and also provide insight into the structure-function relationship of CBLB protein.
authors.affiliation: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Yokoi
authors.forename: Yuuka
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: He-Yao
authors.initials: HY
authors.lastname: Wang
authors.forename: Mai
authors.initials: M
authors.lastname: Kitao
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hayashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Someya
authors.forename: Masao
authors.initials: M
authors.lastname: Kanamori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Naoko
authors.initials: N
authors.lastname: Tajima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D009154:Mutation / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl