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* Section of Hematology and Oncology and Department of Medicine, Boston Medical Center,
Department of Pathology, Boston University School of Medicine, and
Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118; and
Division of Basic Science, Fox Chase Cancer Center, Philadelphia, PA 19111
AND-34, a novel GDP exchange factor, is expressed constitutively at
significant levels in murine splenic B cells, but not in murine splenic
T cells or thymocytes. In B cell lines, anti-IgM treatment
up-regulates AND-34 transcript levels. B cell AND-34 associates with
both the docking molecules p130Cas and HEF1. AND-34 binds by its GDP
exchange factor domain to the C terminus of HEF1, a region of HEF1
previously implicated in apoptotic, adhesion, and cell cycle-regulated
signaling. Overexpression of AND-34 in murine B cell lines activates
the Rho family GTPase Cdc42, but not Rac, Rho, RalA, or Rap1.
Consistent with this, a subpopulation of AND-34 overexpressing B cells
have long filamentous actin-containing cellular extensions.
AND-34 overexpression augments both autophosphorylation and kinase
activity of the Cdc42/Rac-responsive serine/threonine kinase PAK1. As
previously reported for lymphoid cells transfected with constitutively
active Cdc42, AND-34 overexpression inhibits SDF-1
-induced B cell
polarization. These studies suggest that p130Cas and HEF1-associated
AND-34 may regulate B cell adhesion and motility through a
Cdc42-mediated signaling pathway.
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