Biochemical Pharmacology p. 551 - 562 (1997)
Update date:2022-08-10
Topics:
Klinker, Jan F.
Seifert, Roland
G proteins mediate signal transfer from receptors to effector systems. In their guanosine 5'-triphosphate (GTP) bound form, G-protein α-subunits activate effector systems. Termination of G-protein activation is achieved by the high-affinity GTPase [E.C. 3.6.1.-] of their α-subunits. Like GTP, inosine 5' -triphosphate (ITP) and xanthosine 5' triphosphate (XTP) can support effector system activation. We studied the interactions of GTP, ITP, and XTP with the retinal G protein, transducin (TD), and with G-proteins in HL-60 leukemia cell membranes. TD hydrolyzed nucleoside 5'-triphosphates (NTPs) in the order of efficacy GTP > ITP > XTP. NTPs eluted TD from rod outer segment disk membranes in the same order of efficacy. ITP and XTP competitively inhibited TD catalyzed GTP hydrolysis. In HL-60 membranes, the chemoattractants N-formyl-L-methionyl-L-leucyl-L- phenylaline (fMLP) and leukotriene B4 (LTB4,) effectively activated GTP and ITP hydrolysis by G(i) proteins. fMLP and LTB4, were at least l0-fold more potent activators of ITPase than of GTPasc. Complement C5a effectively activated the GTPase of G(i)-proteins but was only a weak stimulator of ITPase. The potency of C5a to activate GTP and ITP hydrolysis was similar. The fMLP stimulated GTPase had a lower K(m) value than the fMLP-stimulated ITPase, whereas the opposite was true for the V(max) values. fMLP, C5a, and LTB4 did not stimulate XTP hydrolysis. Collectively, our data show that GTP, ITP, and XTP bind to G-proteins with different affinities, that G-proteins hydrolyze NTPs with different efficacies, and that chemoattractants stimulate GTP and ITP hydrolysis by G(i)-proteins in a receptor-specific manner. On the basis of our results and the data in the literature, we put forward the hypothesis that GTP, ITP, and XTP act as differential signal amplifiers and signal sorters at the G-protein level.
View MoreJingzhou TianHe Sci&Tech Chemical Co., Ltd.
Contact:86-716-8331612
Address:Jiangjin Road, #18, High-grade technology industries development district, Jingzhou city, Hubei province
Hebei Tianxiang Biological & Pharmaceutical Co., Ltd
Contact:86-0312-6615158
Address:No 42 fazhan street qingyuan county
Contact:
Address:308# dongwu avenue dongxihu district wuhan city
Huzhou City Linghu Xinwang Chemical Co.,Ltd.
Contact:86-572-3948695/3945236
Address:huzhou
Jiaxing Taixin Pharmaceutical Chemical Co., Ltd
Contact:0573-82613601
Address:Chemical Park, Jiaxing, Zhejiang, China
Doi:10.1016/0040-4020(95)00226-X
(1995)Doi:10.1149/1.1566413
(2003)Doi:10.1021/acs.orglett.0c03344
(2020)Doi:10.1002/hlca.19800630427
(1980)Doi:10.1039/jr9610002455
(1961)Doi:10.1002/smll.201303329
(2014)