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

Dongpo Cai, Kyriakos N. Felekkis, Richard I. Near, Geraldine M. O'Neill, Jean Maguire Van Seventer, Erica A. Golemis, Adam Lerner

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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, RA1A, 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-1αinduced 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.

Original languageEnglish
Pages (from-to)969-978
Number of pages10
JournalJournal of Immunology
Volume170
Issue number2
Publication statusPublished - 15 Jan 2003

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