Popis: |
Publisher Summary This chapter discusses the biochemical analysis of regulation of Vav, a guanine-nucleotide exchange factor for Rho family of guanosine 5'-triphosphate (GTPase). Ras and Rac GTPases are activated by guanine-nucleotide exchange factors (GEFs) related to the Saccharomyces cerevisiae CDC25 gene product and the Dbl oncoprotein, respectively. Several Ras-GEFs have been described, whereas more than 20 proteins structurally related to the catalytic domain of Dbl have been reported. Vertebrate Ras-GEFs are generally bifunctional molecules possessing both a CDC25-related domain and a Dbl homology (DH) domain. Thus, Ras-GEFs have the potential to activate Ras and Rac family members. For those Dbl-related molecules where GEF activity has been detected, this activity is specific for one or more of the Rho family GTPases. However, many of the Dbl-related molecules (including Vav), when expressed as recombinant proteins, fail to stimulate the release of GDP from Rho proteins in vitro. The chapter describes the biochemical analysis of Vav and the events contributing to the activation of its Rho family-specific GEF activity. |