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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

Authors

  • Cai D
  • Felekkis KN
  • Near RI
  • O'Neill GM
  • van Seventer JM
  • Golemis EA
  • Lerner A

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

January 15, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: P50 CA83638

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