Parvin Bolourani - Department of Microbiology and Immunology, University of British Columbia.
Georg B Spiegelman
Gerald Weeks

Dictyostelium has large number of Ras-superfamily GTPases relative to the complexity of its genome, which makes it an ideal organism for the study of Ras-controlled signaling pathways. In Dictyostelium Ras proteins paticipate in the signal transduction events leading to the regulation of cell division, motility, cytoskeletal organization, and development. Dyctyostelium discoideum contains 14 ras subfamily genes of which six: rasB, rasC, rasD, rasG, rasS and rapl, have been characterized. We investigated the role of RasC and RasG has a role in a variety of vegetative cellular functions, including motility, cytokinesis, and the initiation of development, but the developmental effects were variable. RasC plays an important role during aggregation that has been linked to reduced prodution of cAMP. Recently we discovered that levels of both RasC and RaG showed a rapid and transient increase when aggregation competent cells were stimulated with the chemoattractant cAMP. the observation thar cAMP stimulated RasG activation led us to investigate the role of RasG during early development by isolating stable rasG null strains in AX2 and JH10 backgrounds. Both of these rasG null strains were able to aggregate and develope normally, but the onest of aggregation was consistently delayed by approximately 4 hours relative to the parental wild type strains. In addition, both the adenylyl cyclase (ACA) activation and PKB phosphorylation that occur in response to cAMP were reduced in the rasG null strain. These results indicate that while RasC and RasG slearly have distinct functions, their signaling pathways appear to converge at some point downstream of activation as both signaling pathways affect ACA activity and PKB phosphorylation. To investigate further the functions of RasC and RasG during early development, we have isolated rasC/rasG double null cells. The phenotypic characterization and the early developmental characteristics of the null strains will be discussed.

Dictyostelium; ras; cAMP; adenylyl cyclase; PKB