G alpha 12 differentially regulates Na+-H+ exchanger isoforms

被引:64
作者
Lin, X
VoynoYasenetskaya, TA
Hooley, R
Lin, CY
Orlowski, J
Barber, DL
机构
[1] UNIV CALIF SAN FRANCISCO,DEPT STOMATOL,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,DEPT MOL & CELLULAR PHARMACOL,SAN FRANCISCO,CA 94143
[4] MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA
关键词
D O I
10.1074/jbc.271.37.22604
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
Activation of several GTPases stimulates Na+-H+ exchange, resulting in an increased efflux of intracellular H+. These GTPases include alpha subunits of the heterotrimeric G proteins G(q) and G13, as well as the low molecular weight GTP-binding proteins Ras, Cdc42, and Rho (Hooley, R., Yu, C.-Y., Simon, M., and Barber, D. L. (1996) J. Biol. Chem. 271, 6152-6158). GTPases coupled to the inhibition of Na+-H+ exchange, however, have not been identified. Several neurotransmitters, including somatostatin and dopamine, inhibit Na+-H+ exchange through a guanine-nueleotide dependent mechanism, suggesting the involvement of a GTPase. In this study we determined that mutational activation of the alpha subunit of G12 inhibits the ubiquitously expressed Na+-H+ exchanger isoform, NBE1. Transient expression of mutationally activated Glu12 inhibited serum- and G alpha 13-stimulated NHE1 activity in HEK293 cells and CCL39 fibroblasts. In addition, in NHE-deficient AP1 cells stably expressing specific NHE isoforms, mutationally activated G alpha 12 inhibited NHE1 activity but stimulated activities of the Na+-H+ exchanger (NHE) isoforms NHE2 and NHE3. In contrast, mutationally activated G alpha 13, another member of the G alpha 12/13 family. stimulated all three NHE isoforms. Although previous studies have identified a parallel action of G alpha 12 and G alpha 13 in regulating MAP (mitogen-activated protein) kinases and cell growth, these GTPases have opposing effects on NHE1 activity.
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页码:22604 / 22610
页数:7
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