de la Fuente Miguel A, Kumar Lalit, Lu Bao, Geha Raif S
Division of Immunology, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA.
Mol Cell Biol. 2006 Jul;26(14):5214-25. doi: 10.1128/MCB.00087-06.
The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-gamma (PLC-gamma); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development, proliferation, cytokine secretion, and signaling in response to T-cell receptor (TCR) ligation were all normal in 3BP2(-/-) mice. 3BP2(-/-) mice had increased accumulation of pre-B cells in the bone marrow and a block in the progression of transitional B cells in the spleen from the T1 to the T2 stage, but normal numbers of mature B cells. B-cell proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to B-cell receptor (BCR) ligation were all impaired. These results suggest that 3BP2 is important for BCR, but not for TCR signaling.
衔接蛋白3BP2在淋巴细胞中表达;与Syk/ZAP-70、Vav和磷脂酶C-γ(PLC-γ)结合;并且被认为对T细胞中白细胞介素-2基因转录很重要。为了确定3BP2在淋巴细胞发育和功能中的作用,我们培育出了3BP2基因缺陷型小鼠。在3BP2基因敲除(-/-)小鼠中,T细胞发育、增殖、细胞因子分泌以及对T细胞受体(TCR)连接的信号传导均正常。3BP2(-/-)小鼠骨髓中前B细胞的积累增加,脾脏中过渡性B细胞从T1期到T2期的进展受阻,但成熟B细胞数量正常。对B细胞受体(BCR)连接的反应中,B细胞增殖、细胞周期进程、PLC-γ2磷酸化、钙动员、NF-ATp去磷酸化以及Erk和Jnk激活均受损。这些结果表明3BP2对BCR很重要,但对TCR信号传导不重要。