COSTIMULATION THROUGH CD28 SUPPRESSES T-CELL RECEPTOR-DEPENDENT ACTIVATION OF THE RAS-LIKE SMALL GTPASE RAP1 IN HUMAN T-LYMPHOCYTES

Citation
Ka. Reedquist et Jl. Bos, COSTIMULATION THROUGH CD28 SUPPRESSES T-CELL RECEPTOR-DEPENDENT ACTIVATION OF THE RAS-LIKE SMALL GTPASE RAP1 IN HUMAN T-LYMPHOCYTES, The Journal of biological chemistry, 273(9), 1998, pp. 4944-4949
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4944 - 4949
Database
ISI
SICI code
0021-9258(1998)273:9<4944:CTCSTR>2.0.ZU;2-X
Abstract
Members of the Ras superfamily of small molecular weight GTPases play diverse and critical roles in mediating cellular responses to extracel lular stimuli, including mitogenesis, cytoskeletal maintenance and rea rrangement, and integrin activation. In T lymphocytes, biochemical and genetic evidence demonstrate that Ras plays an essential role in coup ling T cell receptor ligation to signaling cascades required for T cel l proliferation and development. Recent observations that C3G, a guani ne nucleotide exchange factor specific for the Ras-related GTPase Rap1 , is recruited into tyrosine-phosphorylated protein signaling complexe s in activated T cells have suggested that Rap1 may also play a role i n T cell activation, Utilizing a recently developed technique for dete ction of endogenous, GTP-bound Rap1, we have found that Rap1, but not Rapa, is transiently activated following T cell receptor stimulation o f normal human T lymphocytes, Increases in intracellular calcium is bo th necessary and sufficient to induce Rap1 activation, Remarkably, cos timulation of T cells with mitogenic anti-CD28 antibody completely abo lished T cell receptor-dependent activation of Rap1, This report demon strates a potential role for Rap1 in T cell receptor signaling and sug gests inactivation of Rap1 as a candidate target of CD28-dependent cos timulatory signals required for T cell antigen responsiveness.