Albright C F, Giddings B W, Liu J, Vito M, Weinberg R A
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
EMBO J. 1993 Jan;12(1):339-47. doi: 10.1002/j.1460-2075.1993.tb05662.x.
ras-related GTPases participate in signaling for a variety of cellular processes. The GTPases cycle between a GTP-bound active state and a GDP-bound inactive state. This cycling is partially controlled by guanine nucleotide dissociation stimulators (GDS, also known as exchange factors). We report on the molecular cloning of cDNAs encoding a new mammalian GDS protein, using sequences derived from the yeast ras GDS proteins as probes. The encoded protein stimulates the dissociation of guanine nucleotides from the ras-related ralA and ralB GTPases at a rate at least 30-fold faster than the intrinsic nucleotide dissociation rate. This new GDS, ralGDS, is at least 20-fold more active on the ralA and ralB GTPases than on any other GTPase tested, including other members of the ras family (H-ras, N-ras, K-ras, R-ras, rap1a and rap2), members of the rho family (rhoA, rhoB and CDC42-Hs) and members of the rab family (rab3a and ypt1). While the ralGDS protein is phosphorylated on serine residues, we find no evidence that phosphorylation affects the activity of insect cell-expressed ralGDS towards the ralA or ralB GTPase. The 3600 nucleotide ralGDS mRNA and the 115 kDa protein were found in all tissues and cell lines examined.
Ras相关的GTP酶参与多种细胞过程的信号传导。GTP酶在结合GTP的活性状态和结合GDP的非活性状态之间循环。这种循环部分受鸟嘌呤核苷酸解离刺激因子（GDS，也称为交换因子）控制。我们以酵母ras GDS蛋白的序列为探针，报道了编码一种新的哺乳动物GDS蛋白的cDNA的分子克隆。编码的蛋白刺激鸟嘌呤核苷酸从Ras相关的RalA和RalB GTP酶上解离，其速率比内在核苷酸解离速率至少快30倍。这种新的GDS，即RalGDS，对RalA和RalB GTP酶的活性比对任何其他测试的GTP酶至少高20倍，包括Ras家族的其他成员（H-Ras、N-Ras、K-Ras、R-Ras、Rap1a和Rap2）、Rho家族的成员（RhoA、RhoB和Cdc42-Hs）以及Rab家族的成员（Rab3a和Ypt1）。虽然RalGDS蛋白在丝氨酸残基上被磷酸化，但我们没有发现磷酸化影响昆虫细胞表达的RalGDS对RalA或RalB GTP酶活性的证据。在所检测的所有组织和细胞系中都发现了3600个核苷酸的RalGDS mRNA和115 kDa的蛋白。
