Three differentially expressed Na,K-ATPase alpha subunit isoforms: structural and functional implications.
We have characterized cDNAs coding for three Na,K-ATPase alpha subunit isoforms from the rat, a species resistant to ouabain. Northern blot and S1-nuclease mapping analyses revealed that these alpha subunit mRNAs are expressed in a tissue-specific and developmentally regulated fashion. The mRNA for the alpha 1 isoform, approximately equal to 4.5 kb long, is expressed in all fetal and adult rat tissues examined. The alpha 2 mRNA, also approximately equal to 4.5 kb long, is expressed predominantly in brain and fetal heart. The alpha 3 cDNA detected two mRNA species: a approximately equal to 4.5 kb mRNA present in most tissues and a approximately equal to 6 kb mRNA, found only in fetal brain, adult brain, heart, and skeletal muscle. The deduced amino acid sequences of these isoforms are highly conserved. However, significant differences in codon usage and patterns of genomic DNA hybridization indicate that the alpha subunits are encoded by a multigene family. Structural analysis of the alpha subunits from rat and other species predicts a polytopic protein with seven membrane-spanning regions. Isoform diversity of the alpha subunit may provide a biochemical basis for Na,K-ATPase functional diversity.
Herrera
V L
VL
Laboratory of Molecular and Cellular Cardiology, Howard Hughes Medical Institute, Boston, Massachusetts.
Emanuel
J R
JR
Ruiz-Opazo
N
N
Levenson
R
R
Nadal-Ginard
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D000252:Calcium-Transporting ATPases / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D014018:Tissue Distribution
D008565:Membrane Proteins; D004247:DNA; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase