Linked Life Data

15534861

Source:http://linkedlifedata.com/resource/pubmed/id/15534861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-3-2
pubmed:abstractText
We examined inhibitory effects of external multivalent cations Ni(2+), Co(2+), Cd(2+), La(3+), Mg(2+), and Mn(2+) on reverse-mode exchange of the K(+)-dependent Na(+)/Ca(2+) exchanger NCKX2 and the K(+)-independent exchanger NCX1 expressed in CCL-39 cells by measuring the rate of Ca(2+) uptake with radioisotope tracer and electrophysiological techniques. The apparent affinities for block of Ca(2+) uptake by multivalent cations was higher in NCKX2 than NCX1, and the rank order of inhibitory potencies among these cations was different. Additional experiments also showed that external Li(+) stimulated reverse-mode exchange by NCX1, but not NCKX2 in the presence of 5 mM K(+). Thus, both exchangers exhibited differential sensitivities to not only K(+) but also many other external cations. We attempted to locate the putative binding sites within the alpha motifs for multivalent cations by site-directed mutagenesis experiments. The cation affinities of NCKX2 were altered by mutations of amino acid residues in the alpha-1 motif, but not by mutations in the alpha-2 motif. These results contrast with those for NCX1 where mutations in both alpha-1 and alpha-2 motifs have been shown previously to affect cation affinities. Susceptibility tests with sulfhydryl alkylating agents suggested that the alpha-1 and alpha-2 motifs are situated extracellularly and intracellularly, respectively, in both exchangers. A topological model is proposed in which the extracellular-facing alpha-1 motif forms an external cation binding site that includes key residues N203, G207C, and I209 in NCKX2, while both alpha-1 and alpha-2 motifs together form the binding sites in NCX1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
203
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
420-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15534861-Amino Acid Motifs, pubmed-meshheading:15534861-Amino Acid Sequence, pubmed-meshheading:15534861-Amino Acids, pubmed-meshheading:15534861-Animals, pubmed-meshheading:15534861-Binding, Competitive, pubmed-meshheading:15534861-Binding Sites, pubmed-meshheading:15534861-Cadmium, pubmed-meshheading:15534861-Cations, pubmed-meshheading:15534861-Cell Line, pubmed-meshheading:15534861-Cell Membrane, pubmed-meshheading:15534861-Cobalt, pubmed-meshheading:15534861-Cricetinae, pubmed-meshheading:15534861-Extracellular Space, pubmed-meshheading:15534861-Lanthanum, pubmed-meshheading:15534861-Magnesium, pubmed-meshheading:15534861-Manganese, pubmed-meshheading:15534861-Models, Molecular, pubmed-meshheading:15534861-Molecular Sequence Data, pubmed-meshheading:15534861-Mutation, pubmed-meshheading:15534861-Nickel, pubmed-meshheading:15534861-Potassium, pubmed-meshheading:15534861-Protein Structure, Tertiary, pubmed-meshheading:15534861-Rats, pubmed-meshheading:15534861-Sequence Homology, Amino Acid, pubmed-meshheading:15534861-Sodium-Calcium Exchanger
pubmed:year
2005
pubmed:articleTitle
Different cation sensitivities and binding site domains of Na+-Ca2+-K+ and Na+-Ca2+ exchangers.
pubmed:affiliation
Department of Physiology, School of Medicine, Fukuoka University, 45-1, 7-chrome Nana-kuma, Jonan-ku, Fukuoka 814-0180, Japan. ueharaak@fukuoka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't