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Publication : Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing.

First Author  Nombela-Arrieta C Year  2004
Journal  Immunity Volume  21
Issue  3 Pages  429-41
PubMed ID  15357953 Mgi Jnum  J:93926
Mgi Id  MGI:3510275 Doi  10.1016/j.immuni.2004.07.012
Citation  Nombela-Arrieta C, et al. (2004) Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity 21(3):429-41
abstractText  Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kgamma, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2-/- B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kgamma thus play distinct roles during T and B cell integrin activation and migration.
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