Chen Grace, Dimitriou Ioannis D, La Rose Jose, Ilangumaran Subburaj, Yeh Wen-Chen, Doody Gina, Turner Martin, Gommerman Jennifer, Rottapel Robert
Princess Margaret Hospital/Ontario Cancer Institute, Room 10-105, University Ave., Toronto, ON, Canada.
Mol Cell Biol. 2007 Apr;27(8):3109-22. doi: 10.1128/MCB.01014-06. Epub 2007 Feb 5.
3BP2 is a pleckstrin homology domain- and Src homology 2 (SH2) domain-containing adapter protein that is mutated in the rare human bone disorder cherubism and which has also been implicated in immunoreceptor signaling. However, a function for this protein has yet to be established. Here we show that mice lacking 3BP2 exhibited a perturbation in the peritoneal B1 and splenic marginal-zone B-cell compartments and diminished thymus-independent type 2 antigen response. 3BP2(-/-) B cells demonstrated a proliferation defect in response to antigen receptor cross-linking and a heightened sensitivity to B-cell receptor-induced death via a caspase-3-dependent apoptotic pathway. We show that 3BP2 binds via its SH2 domain to the CD19 signaling complex and is required for optimum Syk phosphorylation and calcium flux.
3BP2是一种含有普列克底物蛋白同源结构域和Src同源结构域2（SH2）的衔接蛋白，在罕见的人类骨骼疾病 cherubism 中发生突变，并且也与免疫受体信号传导有关。然而，该蛋白的功能尚未确定。在这里，我们表明缺乏3BP2的小鼠在腹膜B1和脾脏边缘区B细胞区室中表现出紊乱，并且胸腺非依赖性2型抗原反应减弱。3BP2(-/-) B细胞在对抗抗原受体交联时表现出增殖缺陷，并且通过半胱天冬酶-3依赖性凋亡途径对B细胞受体诱导的死亡敏感性增强。我们表明，3BP2通过其SH2结构域与CD19信号复合物结合，并且是最佳Syk磷酸化和钙流所必需的。
