Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IDENTIFICATION OF SITES REQUIRED FOR DOWN-REGULATION OF NA+ H+ EXCHANGER NHE3 ACTIVITY BY CAMP-DEPENDENT PROTEIN-KINASE - PHOSPHORYLATION-DEPENDENT AND PHOSPHORYLATION-INDEPENDENT MECHANISMS/
Autore:
KURASHIMA K; YU FH; CABADO AG; SZABO EZ; GRINSTEIN S; ORLOWSKI J;
Indirizzi:
MCGILL UNIV,DEPT PHYSIOL,3655 DRUMMOND ST,MCINTYRE MED SCI BLDG MONTREAL PQ H3G 1Y6 CANADA MCGILL UNIV,DEPT PHYSIOL MONTREAL PQ H3G 1Y6 CANADA HOSP SICK CHILDREN,RES INST,DIV CELL BIOL TORONTO ON M5G 1X8 CANADA
Titolo Testata:
The Journal of biological chemistry
fascicolo: 45, volume: 272, anno: 1997,
pagine: 28672 - 28679
SICI:
0021-9258(1997)272:45<28672:IOSRFD>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTESTINAL ELECTROLYTE TRANSPORT; INTRACELLULAR PH; H+ EXCHANGER; DIARRHEAL DISEASE; PROXIMAL TUBULES; NA/H EXCHANGER; CELLS; ISOFORM; SENSITIVITY; RECOGNITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
K. Kurashima et al., "IDENTIFICATION OF SITES REQUIRED FOR DOWN-REGULATION OF NA+ H+ EXCHANGER NHE3 ACTIVITY BY CAMP-DEPENDENT PROTEIN-KINASE - PHOSPHORYLATION-DEPENDENT AND PHOSPHORYLATION-INDEPENDENT MECHANISMS/", The Journal of biological chemistry, 272(45), 1997, pp. 28672-28679

Abstract

We recently identified a region within the cytoplasmic C-terminal tail of the Na+/H+ exchanger NHE3 isoform (residues 579 to 684) which is essential for inhibition of transport activity by cAMP-dependent protein kinase (PKA) (Cabado, A. G., Yu, F. H., Rapus, A., Gergely, L., Grinstein, S., and Orlowski, J. (1996) J. Biol. Chem. 271, 3590-3599). Tofurther define determinants of PKA regulation, six serine residues located in potential recognition sequences for PKA within, or adjacent to, this region (positions 552, 605, 634, 661, 690, and 691) were altered either independently or in various combinations using site-directedmutagenesis. Wild type and mutant NHE3s tagged with the influenza virus hemagglutinin epitope were stably expressed in exchanger-deficient Chinese hamster ovary cells (AP-1) for functional studies. Of the individual mutations examined, only substitutions at Ser(605) or Ser(634) affected sensitivity to forskolin, an activator of adenylate cyclase, although partial inhibition of NHE3 activity by forskolin remained. Bycontrast, simultaneous mutation of both these serines completely abolished cAMP-mediated inhibition of NHE3 without greatly affecting basaltransport activity. Two-dimensional analysis of tryptic digests of immunoprecipitated NHE3 labeled in vivo with [P-32]orthophosphate revealed several phosphopeptides under basal conditions. Phosphorylation wasincreased approximately 3-fold in one of these peptides following forskolin treatment, and this change was eliminated by mutation of residue Ser(605). Thus, phosphorylation of Ser(605) is essential for cAMP-mediated inhibition of NHE3. In addition, Ser(634) is also required for the effect of cAMP, even though this residue does not become phosphorylated upon activation of PKA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:31:15