Two new members of a family of Ypt/Rab GTPase activating proteins - Promiscuity of substrate recognition

被引:78
作者
Albert, S [1 ]
Gallwitz, D [1 ]
机构
[1] Max Planck Inst Biophys Chem, Dept Mol Genet, D-37070 Gottingen, Germany
关键词
D O I
10.1074/jbc.274.47.33186
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M), 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.
引用
收藏
页码:33186 / 33189
页数:4
相关论文
共 29 条
[1]   Structural differences in the minimal catalytic domains of the GTPase-activating proteins p120(GAP) and neurofibromin [J].
Ahmadian, MR ;
Wiesmuller, L ;
Lautwein, A ;
Bischoff, FR ;
Wittinghofer, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (27) :16409-16415
[2]   Identification of the catalytic domains and their functionally critical arginine residues of two yeast GTPase-activating proteins specific for Ypt/Rab transport GTPases [J].
Albert, S ;
Will, E ;
Gallwitz, D .
EMBO JOURNAL, 1999, 18 (19) :5216-5225
[3]  
BI E, IN PRESS MOL BIOL CE
[4]   PROTEINS REGULATING RAS AND ITS RELATIVES [J].
BOGUSKI, MS ;
MCCORMICK, F .
NATURE, 1993, 366 (6456) :643-654
[5]   Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which associates with the centrosome [J].
Cuif, MH ;
Possmayer, F ;
Zander, H ;
Bordes, N ;
Jollivet, F ;
Couedel-Courteille, A ;
Janoueix-Lerosey, I ;
Langsley, G ;
Bornens, M ;
Goud, B .
EMBO JOURNAL, 1999, 18 (07) :1772-1782
[6]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395
[7]   Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family [J].
Du, LL ;
Collins, RN ;
Novick, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (06) :3253-3256
[8]   EXPERIMENTAL-DESIGNS FOR ESTIMATING THE PARAMETERS OF THE MICHAELIS-MENTEN EQUATION FROM PROGRESS CURVES OF ENZYME-CATALYZED REACTIONS [J].
DUGGLEBY, RG ;
CLARKE, RB .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1080 (03) :231-236
[9]   Sec3p is a spatial landmark for polarized secretion in budding yeast [J].
Finger, FP ;
Hughes, TE ;
Novick, P .
CELL, 1998, 92 (04) :559-571
[10]   Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product [J].
Frech, M ;
John, J ;
Pizon, V ;
Chardin, P ;
Tavitian, A ;
Clark, R ;
Mccormick, F ;
Wittinghofer, A .
SCIENCE, 1990, 249 (4965) :169-171