G-PROTEIN REGULATION OF THE NA+/H+ ANTIPORTER IN XENOPUS-LAEVIS OOCYTES - INVOLVEMENT OF PROTEIN-KINASE-A AND PROTEIN-KINASE-C

被引:25
作者
BUSCH, S
WIELAND, T
ESCHE, H
JAKOBS, KH
SIFFERT, W
机构
[1] UNIV ESSEN GESAMTHSCH, INST PHARMAKOL, D-45122 ESSEN, GERMANY
[2] UNIV ESSEN GESAMTHSCH, INST MOLEK BIOL, D-45122 ESSEN, GERMANY
关键词
D O I
10.1074/jbc.270.30.17898
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
We have characterized the regulation of the endogenous Na+/H+ exchanger in Xenopus laevis oocytes by G proteins and protein kinases by measuring the ethylisopropylamiloride-sensitive Li+ uptake. Injection of oocytes with the stable GTP analog GTP gamma S stimulated Li+ uptake up to almost 4-fold, an effect blocked by coinjection with the GDP analog guanyl-5'-yl thiophosphate. Injection into oocytes of beta gamma subunits of the heterotrimeric G protein transducin enhanced Li+ uptake by about 3-fold. This stimulation was blocked by transducin alpha subunits, which by themselves did not influence Li+ uptake. Using various activators and inhibitors of protein kinases, it is demonstrated that the X. laevis oocyte Na+/H+ antiporter can be stimulated by activation of both protein kinase A and C. Stimulation of Na+/H+ exchanger activity by GTP gamma S but not that induced by transducin beta gamma subunits was blocked by the protein kinase A inhibitor H-89. On the other hand, transducin beta gamma subunit-stimulated activity was prevented by the protein kinase C inhibitor, calphostin C. The non-selective protein kinase inhibitor H-7 blocked both GTP gamma S- and transducin beta gamma subunit-stimulated Na+/H+ exchanger activity. The results suggest that the Na+/H+ exchanger of X. laevis oocytes can be activated by G proteins and that this activation is not direct but mediated by protein kinase A- and/or protein kinase C-dependent pathways.
引用
收藏
页码:17898 / 17901
页数:4
相关论文
共 30 条