Protein-tyrosine phosphatase SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of B cell antigen receptor activation
Protein-tyrosine phosphatase SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of B cell antigen receptor activation
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DOI：
10.1074/jbc.272.32.20038
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发表时间：
1997-08-08
影响因子：
4.8
通讯作者：
Neel, BG
中科院分区：
文献类型：
--
作者：
Nadler, MJS;Chen, BB;Neel, BG
抑制性铁受体Fc γ RIIB提供一个信号，终止B细胞抗原受体的激活，阻断细胞外钙的内流。由于蛋白酪氨酸磷酸酶SHP-1结合酪氨酸1磷酸化的Fc γ RIIB和Fc γ RIIB介导的抑制在不表达SHP-1的母鼠（me/me）中存在缺陷，因此有人提出SHP-1介导B细胞中的Fc γ RIIB信号传导（D'Ambrosio， D., Hippen， K. L., Minskoff S. A., Mellman， I., Pani， G., Siminovitch， K. A.和Cambier， J. C. (1995) Science 268, 283 -297）。然而，SHP-1对于肥大细胞中Fc γ RIIB介导的Fc epsilon RI信号的抑制是必不可少的（One， M., Bolland， S., Tempst， P.，和Ravetch， J. V. (1996) Nature 383, 263-266），这促使我们重新研究SHP-1在B细胞中Fc γ RIIB信号传导中的作用。我们从me/me小鼠和正常胎鼠身上获得了永生化的sIgM+、Fc γ RIIB+细胞系。Fc γ RIIB和sIgM抗原受体的共连接可抑制两种细胞系中的钙内流。用抗Fc γ RIIB抗体预孵育可逆转抑制，表明它是由Fc γ RIIB介导的。在这两种细胞系中，肌醇5′磷酸酶SHIP被招募到酪氨酸磷酸化Fc γ RIIB， Fc γ RIIB介导的CD19去磷酸化也发生在存在或不存在SHP-1的情况下。我们的研究结果证实，在Fc γ RIIB介导的sIgM抗原受体信号传导抑制中，SHP-1是必不可少的。
The inhibitory Fe receptor, Fc gamma RIIB, provides a signal that aborts B cell antigen receptor activation, blocking extracellular calcium influx. Because the protein-tyrosine phosphatase SHP-1 binds tyrosy1 phosphorylated Fc gamma RIIB and Fc gamma RIIB-mediated inhibition is defective in motheaten (me/me) mice, which do not express SHP-1, it was proposed that SHP-1 mediates Fc gamma RIIB signaling in B cells (D'Ambrosio, D., Hippen, K. L., Minskoff S. A., Mellman, I., Pani, G., Siminovitch, K. A., and Cambier, J. C. (1995) Science 268, 293-297). However, SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of Fc epsilon RI signaling in mast cells (One, M., Bolland, S., Tempst, P., and Ravetch, J. V. (1996) Nature 383, 263-266), prompting us to re-examine the role of SHP-1 in Fc gamma RIIB signaling in B cells. We generated immortalized sIgM+, Fc gamma RIIB+ cell lines from me/me mice and normal littermates. Co-Ligation of Fc gamma RIIB and the sIgM antigen receptor inhibits calcium influx in both cell lines. Inhibition is reversed by preincubation with anti-Fc gamma RIIB antibodies, indicating that it is mediated bg Fc gamma RIIB. The inositol 5' phosphatase SHIP is recruited to tyrosyl-phosphorylated Fc gamma RIIB in both cell Lines, Fc gamma RIIB-mediated CD19 dephosphorylation also occurs in the presence or the absence of SHP-1, Our results establish that SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of sIgM antigen receptor signaling.