title: Regulation of the renal Na(+)-H+ exchanger by calcium calmodulin-dependent multifunctional protein kinase II.
abstract: Prior studies indicate that cAMP-dependent protein kinase (PKA) and calcium calmodulin-dependent multifunctional protein kinase II (CaM-KII) inhibit Na(+)-H+ exchanger as assayed in octyl glucoside solubilized rabbit renal brush border membrane proteins reconstituted into artificial lipid vesicles. An anion exchange chromatography fraction of these proteins which elutes between 0.2 and 0.4 M NaCl (Fraction B), however, fails to demonstrate regulation of the transporter by PKA. The present studies examine regulation of the Na(+)-H+ exchanger by CaM-KII using Fraction B proteins. As compared to the initial total protein extract, Fraction B demonstrated increased Na(+)-H+ exchange activity. CaM-KII inhibited the Na(+)-H+ exchanger in Fraction B by 38.2 +/- 10.6% in an ATP and calmodulin-dependent manner. The results of the present studies suggest that CaM-KII-mediated inhibition of the Na(+)-H+ exchanger involves the phosphorylation of different polypeptides than those mediating the inhibition of this transporter by PKA.
authors.affiliation: Department of Medicine, University of California, Los Angeles.
authors.forename: E
authors.initials: E
authors.lastname: Weinman
authors.forename: R
authors.initials: R
authors.lastname: Hanley
authors.forename: G
authors.initials: G
authors.lastname: Morell
authors.forename: N
authors.initials: N
authors.lastname: Yuan
authors.forename: D
authors.initials: D
authors.lastname: Steplock
authors.forename: G
authors.initials: G
authors.lastname: Bui
authors.forename: S
authors.initials: S
authors.lastname: Shenolikar
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008081:Liposomes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002147:Calmodulin; D002352:Carrier Proteins; D008081:Liposomes; D017923:Sodium-Hydrogen Exchangers; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D002118:Calcium