Sci. Signal., 17 July 2012
EnAbling T Cell MigrationTo perform their role in immune surveillance and protective immunity, T cells must continuously circulate through the blood and secondary lymphoid organs (during homeostasis), as well as migrate to sites of inflammation. T cell migration is stimulated by chemokines, which activate small GTPases, including Rap1, that lead to cellular polarization and actin rearrangement. Gu et al. found that the tyrosine kinases Abl and Arg connected chemokine receptor stimulation to Rap1 activation through a pathway that involved the adaptor protein HEF1. Loss of both Abl and Arg in mouse T cells inhibited their homeostatic migration as well as their recruitment to inflammatory sites in vivo. Together, these data suggest that Abl family kinases may provide therapeutic targets for the treatment of inflammatory diseases that are chemokine-dependent.
Citation: J. J. Gu, C. P. Lavau, E. Pugacheva, E. J. Soderblom, M. A. Moseley, A. M. Pendergast, Abl Family Kinases Modulate T Cell–Mediated Inflammation and Chemokine-Induced Migration Through the Adaptor HEF1 and the GTPase Rap1. Sci. Signal. 5, ra51 (2012).
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