HUMAN SPA-1 GENE-PRODUCT SELECTIVELY EXPRESSED IN LYMPHOID-TISSUES ISA SPECIFIC GTPASE-ACTIVATING PROTEIN FOR RAP1 AND RAP2 - SEGREGATE EXPRESSION PROFILES FROM A RAP1GAP GENE-PRODUCT

Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation , Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA e ncodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regi ons and rap1GAP-related domain followed by a coiled coil stretch. Bacu lovirally expressed p130(SPA-1) exhibited GTPase-activating protein (G AP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Pac, and Ran, with comparable specific activity to the rap1GAP gene product (p8 5/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2, Expres sion of SPA-1 and rap1GAP genes tended to be segregate in various tiss ues, lymphoid tissues expressing abundant SPA-1 transcript without rap 1GAP, while those such as brain, kidney, and pancreas exhibiting rap1G AP mRNA with little SPA-1, Promyelocytic HL-60 cells, which expressed p130(SPA-1) With little p85/95(rap1GAP) in uninduced state, showed pro gressive decline in p130(SPA-1) and conversely drastic increase in p85 /95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results su ggested that products of SPA-1 and rap1GAP genes, albeit comparable GA P activity for Rap1 and Rap2, functioned in the distinct contexts depe nding on cell types and/or states.