The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and activates Cdc42.

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-1alpha-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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, B-Lymphocytes, Cell Line, Cell Polarity, Chemokine CXCL12, Chemokines, CXC, Crk-Associated Substrate Protein, Cross-Linking Reagents, Guanine Nucleotide Exchange Factors, Humans, Immunoglobulin M, Mice, Mice, Inbred BALB C, Peptide Fragments, Phosphoproteins, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Proteins, Receptors, Antigen, B-Cell, Retinoblastoma-Like Protein p130, Transcription, Genetic, Up-Regulation, cdc42 GTP-Binding Protein, p21-Activated Kinases
J. Immunol.
Date: Jan. 15, 2003
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