title: The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and activates Cdc42.
abstract: 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.
authors.affiliation: Section of Hematology and Oncology and Department of Medicine, Boston Medical Center, Boston University School of Medicine, MA 02118, USA.
authors.forename: Dongpo
authors.initials: D
authors.lastname: Cai
authors.forename: Kyriakos N
authors.initials: KN
authors.lastname: Felekkis
authors.forename: Richard I
authors.initials: RI
authors.lastname: Near
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Neill
authors.forename: Jean Maguire
authors.initials: JM
authors.lastname: van Seventer
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
authors.forename: Adam
authors.initials: A
authors.lastname: Lerner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000502:physiology; D050719:Crk-Associated Substrate Protein; D003432:Cross-Linking Reagents / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D054462:p21-Activated Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493841:BCAR1 protein, human; C493842:Bcar1 protein, mouse; C120867:Bcar3 protein, mouse; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D050719:Crk-Associated Substrate Protein; D003432:Cross-Linking Reagents; C515256:Cxcl12 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D007075:Immunoglobulin M; C099942:NEDD9 protein, human; D010446:Peptide Fragments; D010750:Phosphoproteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D050717:Retinoblastoma-Like Protein p130; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein