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. 2011 Dec;112(12):3666-74.
doi: 10.1002/jcb.23300.

Discoidin domain receptor 1 expression in activated T cells is regulated by the ERK MAP kinase signaling pathway

Nizar Chetoui  1 , Mohammed-Amine El Azreq, Marc Boisvert, Marie-Ève Bergeron, Fawzi Aoudjit
Affiliations

Discoidin domain receptor 1 expression in activated T cells is regulated by the ERK MAP kinase signaling pathway

Nizar Chetoui et al. J Cell Biochem. 2011 Dec.

Abstract

The expression and function of discoidin domain receptor 1 (DDR1) in T cells are still poorly explored. We have recently shown that activation of primary human T cells via their T cell receptor leads to increased expression of DDR1, which promoted their migration in three-dimensional collagen. In the present study, we provide evidence that activated T cells bind collagen through DDR1. We found that the DDR1:Fc blocking molecule significantly reduced the ability of activated T cells to bind soluble biotinylated collagen. However, DDR1:Fc had no impact on the adhesion of activated T cells to collagen and overexpression of DDR1 in Jurkat T cells did not enhance their adhesion. Together, our results indicate that DDR1 can promote T cell migration without enhancing adhesion to collagen, suggesting that it can contribute to the previously described amoeboid movement of activated T cells in collagen matrices. Our results also show that CD28, in contrast to IL-2 expression, did not costimulate the expression of DDR1 in primary human T cells. Using specific inhibitors, we demonstrated that TCR-induced expression of DDR1 in T cells is regulated by the Ras/Raf/ERK MAP Kinase and PKC pathways but not by calcium/calcineurin signaling pathway or the JNK and P38 MAP Kinases. Thus, our study provides additional insights into the physiology of DDR1 in T cells and may therefore further our understanding of the regulatory mechanisms of T cell migration.

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