Two new members of a family of Ypt/Rab GTPase activating proteins. Promiscuity of substrate recognition.
Monomeric GTPases of the Ras superfamily have a very slow intrinsic GTPase activity which is accelerated by specific GTPase-activating proteins. In contrast to Ras- and Rho-specific GTPase-activating proteins (GAPs) that have been studied in great detail, little is known about the functioning of GAPs specific for Ypt/Rab transport GTPases. We have identified two novel Ypt/Rab-GAPs because of their sequence relatedness to the three known GAPs Gyp1p, Gyp6p, and Gyp7p. Mdr1/Gyp2p is an efficient GAP for Ypt6p and Sec4p, whereas Msb3/Gyp3p is a potent GAP for Sec4p, Ypt6p, Ypt51p, Ypt31/Ypt32p, and Ypt1p. Although the affinity of Msb3/Gyp3p for its preferred substrate Sec4p is low (K(m) = 154 microM), it accelerates the intrinsic GTPase activity of Sec4p 5 x 10(5)-fold. Msb3/Gyp3p appears to be functionally linked to Cdc42p-regulated pathway(s). The results demonstrate that in yeast there is a large family of Ypt/Rab-GAPs, members of which discriminate poorly between GTPases involved in regulating different steps of exo- and endocytic transport routes.
Albert
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Max Planck Institute for Biophysical Chemistry, Department of Molecular Genetics, D-37070 Göttingen, Germany.
Gallwitz
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D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
D017931:DNA Primers; D020558:GTP Phosphohydrolases; D020691:rab GTP-Binding Proteins