Kikuchi A, Kuroda S, Sasaki T, Kotani K, Hirata K, Katayama M, Takai Y
Department of Biochemistry, Kobe University School of Medicine, Japan.
J Biol Chem. 1992 Jul 25;267(21):14611-5.
smg GDS and rho GDI are stimulatory and inhibitory GDP/GTP exchange proteins, respectively, for a group of ras p21-related small GTP-binding proteins (G proteins). rho p21 is a common substrate small G protein for both GDP/GTP exchange proteins. We examined here the functional interactions of these GDP/GTP exchange proteins with rho p21 as a substrate. smg GDS and rho GDI interacted with the GDP-bound form of rho p21 and thereby stimulated and inhibited, respectively, the dissociation of GDP. The inhibitory effect of rho GDI was much stronger than the stimulatory effect of smg GDS. The GDP-bound form of rho p21 formed a complex with rho GDI but not with smg GDS in their simultaneous presence. Since the content of smg GDS was generally less than that of rho GDI in cells, these results suggest that there is some mechanism to release the inhibitory action of rho GDI and to make rho p21 sensitive to the smg GDS action during the conversion of rhoA p21 from the GDP-bound inactive form to the GTP-bound active form in intact cells. On the other hand, rho p21 was previously shown to be ADP-ribosylated by bacterial ADP-ribosyltransferases, named C3 and EDIN, at Asn41 in the putative effector region of rho p21. This ADP-ribosylation was inhibited by rho GDI much more efficiently than by smg GDS. These results suggest that rho GDI may mask the putative effector region of rho p21 and thereby inhibit its interaction with the target protein even in the presence of smg GDS. Thus, both smg GDS and rho GDI are important to regulate the rho p21 activity and action in cooperation with each other.
smg GDS和rho GDI分别是一组与ras p21相关的小GTP结合蛋白（G蛋白）的刺激性和抑制性GDP / GTP交换蛋白。rho p21是这两种GDP / GTP交换蛋白共同的底物小G蛋白。我们在此研究了这些GDP / GTP交换蛋白与作为底物的rho p21之间的功能相互作用。smg GDS和rho GDI与GDP结合形式的rho p21相互作用，从而分别刺激和抑制GDP的解离。rho GDI的抑制作用比smg GDS的刺激作用强得多。在它们同时存在的情况下，GDP结合形式的rho p21与rho GDI形成复合物，但不与smg GDS形成复合物。由于细胞中smg GDS的含量通常低于rho GDI的含量，这些结果表明，在完整细胞中rhoA p21从GDP结合的无活性形式转变为GTP结合的活性形式的过程中，存在某种机制来解除rho GDI的抑制作用，并使rho p21对smg GDS的作用敏感。另一方面，先前已表明rho p21在rho p21假定的效应区域中的Asn41处被名为C3和EDIN的细菌ADP核糖基转移酶进行ADP核糖基化。这种ADP核糖基化被rho GDI抑制的效率比被smg GDS抑制的效率高得多。这些结果表明，rho GDI可能掩盖了rho p21的假定效应区域，从而即使在存在smg GDS的情况下也抑制其与靶蛋白的相互作用。因此，smg GDS和rho GDI对于相互协作调节rho p21的活性和作用都很重要。
