FcγRIIb-mediated negative regulation of BCR signalling is associated with the recruitment of the MAPkinase-phosphatase, Pac-1, and the 3′-inositol phosphatase, PTEN
FcγRIIb-mediated negative regulation of BCR signalling is associated with the recruitment of the MAPkinase-phosphatase, Pac-1, and the 3′-inositol phosphatase, PTEN
复制标题
DOI：
10.1016/s0898-6568(03)00113-x
复制
发表时间：
2004-01-01
影响因子：
4.8
通讯作者：
Harnett, MM
中科院分区：
文献类型：
--
作者：
Brown, KS;Blair, D;Harnett, MM
IgG的低亲和力受体FcgammaRIIb负调控B细胞抗原受体（BCR）介导的增殖信号传导。据报道，FcgammaRIIb通过将BCR从RasMAPkinase通路解偶联来介导这种抑制。我们现在表明，fcgammariib介导的负反馈抑制也与Erk相关的磷酸酶活性的诱导相关，这反映了Erk和MAPkinase磷酸酶Pac-1的快速关联，以及ErkMAPkinase的去磷酸化和失活。因此，这种取消正在进行的erkmap激酶信号传导的机制为免疫复合物介导的活性抗原驱动B细胞反应的快速反馈抑制提供了理论依据。此外，FcgammaRIIb信号传导还诱导3'-肌醇磷酸酶PTEN的募集和激活，PTEN通过拮抗PI 3kinase活性和抑制bcr -偶联抗凋亡激酶Akt，为FcgammaRIIb介导的bcr -偶联ErkMAPkinase、细胞存活和增殖的负调控提供了另一种机制。(C) 2003 Elsevier Inc.版权所有。
The low-affinity receptor for IgG, FcgammaRIIb, negatively regulates B cell antigen receptor (BCR)-mediated proliferative signalling. FcgammaRIIb has been reported to mediate this inhibition by uncoupling the BCR from the RasMAPkinase pathway. We now show that FcgammaRIIb-mediated negative feedback inhibition also correlates with induction of an Erk-associated phosphatase activity that reflects the rapid association of Erk and the MAPkinase phosphatase, Pac-1, and dephosphorylation and inactivation of ErkMAPkinase. This mechanism of abrogating ongoing ErkMAPkinase signalling therefore provides a rationale for rapid immune-complex-mediated feedback inhibition of active antigen-driven B cell responses. In addition, FcgammaRIIb signalling also induces the recruitment and activation of the 3'-inositol phosphatase, PTEN, which by antagonising PI 3kinase activity and inhibiting BCR-coupling to the anti-apoptotic kinase, Akt, provides an additional mechanism for FcgammaRIIb-mediated negative regulation of BCR-coupling to ErkMAPkinase, cell survival and proliferation. (C) 2003 Elsevier Inc. All rights reserved.