BIOLOGICAL CHARACTERIZATION OF DROSOPHILA RAPGAP1, A GTPASE-ACTIVATING PROTEIN FOR RAP1

The activity of Pas family proteins is modulated irt vivo by the funct ion of GTPase activating proteins, which increase their intrinsic rate of GTP hydrolysis, We have isolated cDNAs encoding a GAP for the Dros ophila Rap1 GTPase, Drosophila Rapgap1 encodes an 850-amino acid prote in with a central region that displays substantial sequence similarity to human RapGAP, This domain, when expressed in Escherichia coil, pot ently stimulates Rap1 GTPase activity in vitro, Unlike Rap1, which is ubiquitously expressed, Rapgap1 expression is highly restricted, Rapga p1 is expressed at high levels in the developing photoreceptor cells a nd in the optic lobe, Rapgap1 mRNA is also localized in the pole plasm in an oskar-dependent manner, Although mutations that completely abol ish Rapgap1 function display no obvious phenotypic abnormalities, over expression of Rapgap1 induces a rough eye phenotype that is exacerbate d by reducing Rap1 gene dosage, Thus, Rapgap1 can function as a negati ve regulator of Rap1-mediated signaling in vivo.