Journal
MOLECULAR IMMUNOLOGY
Volume 43, Issue 10, Pages 1687-1693Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2005.09.010
Keywords
integrin; protein phosphatase; ERK/MAP kinase; T cells
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Growing evidence indicates that interactions of T cells with extracellular matrix through beta 1 integrins are important for the regulation of T cell-mediated immune responses and diseases. In this regard, we have recently demonstrated that collagen 1 (Coll 1) through alpha 2 beta 1 integrin inhibited Fas-induced apoptosis of T cells by activating a protein phosphatase 2A (PP2A)-dependent ERK/MAP Kinase pathway. As Survival of T cells is critical for their functions. we further investigated the mechanisms underlying the activation of this pathway. Inhibition studies demonstrated that Coll I activates the ERK/MAP Kinase pathway in Jurkat T cells through the activation of Ras and Raf-1. Activation of PP2A was not necessary for the binding of Coll I to Jurkat T cells, but is required for the activation of Raf-1. In accordance, activation of Ras, Raf-1 and PP2A were also required for the ability of Coll I to protect Jurkat T cells from Fas-induced apoptosis. In contrast and despite its capacity to activate Ras, fibronectin (Fbn) failed to activate PP2A and Raf-1. These results might explain, at least in part, the weak ability of Fbn to activate ERK in T cells, supporting thus the differential signaling of beta 1 integrin members in these cells. This study provides novel insights into the mechanisms by which P I integrins activate the ERK/MAP Kinase pathway in T cells, and is the first report to provide a role for PP2A in integrin-mediated ERK/MAP Kinase activation. (c) 2005 Elsevier Ltd. All rights reserved.
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