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.
Pubmed ID: 12517963 RIS Download
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