adaptor skap-55 binds p21ras activating exchange factor rasgrp1 and negatively regulates the p21ras-erk pathway in t-cells适配器skap-55结合p21ras激活交换因子rasgrp1和负调节t细胞p21ras-erk通路.pdfVIP

Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells 1,2. 2,3. 2,4 1,2 3 2 Helga Schneider , Hongyan Wang , Monika Raab , Elke Valk , Xin Smith , Matt Lovatt , 1,2 1 4 1,2,3 Zhonglin Wu , Braudel Maqueira-Iglesias , Klaus Strebhardt , Christopher E. Rudd * 1 Cell Signalling Section, Department of Pathology, University of Cambridge, Cambridge, United Kingdom, 2 Molecular Immunology Section, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom, 3 Cambridge Institute for Medical Research, Cambridge, United Kingdom, 4 Department of Gynecology and Obstetrics, Medical School, Johann Wolfgang Goethe-University, Frankfurt, Germany Abstract While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper- activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an