کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2832914 | 1163851 | 2006 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Collagen type I-mediated activation of ERK/MAP Kinase is dependent on Ras, Raf-1 and protein phosphatase 2A in Jurkat T cells Collagen type I-mediated activation of ERK/MAP Kinase is dependent on Ras, Raf-1 and protein phosphatase 2A in Jurkat T cells](/preview/png/2832914.png)
Growing evidence indicates that interactions of T cells with extracellular matrix through β1 integrins are important for the regulation of T cell-mediated immune responses and diseases. In this regard, we have recently demonstrated that collagen I (Coll I) through α2β1 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 β1 integrin members in these cells. This study provides novel insights into the mechanisms by which β1 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.
Journal: Molecular Immunology - Volume 43, Issue 10, April 2006, Pages 1687–1693