PAK1向免疫突触的动态募集由PIX介导，与SLP-76和Vav1无关。

Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1.

作者信息

Phee Hyewon, Abraham Robert T, Weiss Arthur

机构信息

Department of Medicine, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, 94143, USA.

出版信息

Nat Immunol. 2005 Jun;6(6):608-17. doi: 10.1038/ni1199. Epub 2005 May 1.

DOI:10.1038/ni1199

PMID:15864311

Abstract

T cell receptor engagement activates p21-activated kinase 1 (PAK1) through a LAT-SLP-76-Nck-Vav-Rac-dependent pathway. A second independent pathway involving a GIT-PIX-PAK1 trimolecular complex is also activated by T cell receptor ligation. Here we show a Vav-independent pathway exists that leads to PAK1 activation. In addition, PAK1, PIX and GIT1 were recruited to the T cell-antigen-presenting cell contact site independently of SLP-76 and Vav1. PAK1 recruitment to the T cell-antigen-presenting cell interface required interaction with PIX, which also led to optimal PLC-gamma1 activation and T cell receptor-dependent transcriptional responses. These data indicate that a pathway involving the GIT-PIX-PAK1 complex has a crucial function in PAK1 activation by recruiting PAK1 to the immunological synapse.

摘要

T细胞受体的结合通过一条依赖LAT-SLP-76-Nck-Vav-Rac的途径激活p21激活激酶1（PAK1）。第二条独立的途径，涉及GIT-PIX-PAK1三分子复合物，也可被T细胞受体连接激活。在此我们表明存在一条不依赖Vav的导致PAK1激活的途径。此外，PAK1、PIX和GIT1被招募到T细胞-抗原呈递细胞接触部位，且不依赖于SLP-76和Vav1。PAK1被招募到T细胞-抗原呈递细胞界面需要与PIX相互作用，这也导致了最佳的PLC-γ1激活和T细胞受体依赖性转录反应。这些数据表明，涉及GIT-PIX-PAK1复合物的途径在通过将PAK1招募到免疫突触而激活PAK1过程中具有关键作用。