alar4, a constitutive mutant of the A system for amino acid transport, has increased abundance of the Na+,K+-ATPase and mRNA for alpha 1 subunit of this enzyme.

A constitutive mutant, alar4, for the A system of amino acid transport, has increased activity and amount of the A system. This is accompanied by increased sensitivity to ouabain, as measured by efficiency of plating, and increased activity and abundance of the Na+,K+-ATPase that is present in the parental cell line, CHO-K1 (wild type). The latter was shown by increases in (i) ouabain-inhibitable 86Rb uptake in intact cells, (ii) ouabain-inhibitable ATPase activity in mixed membrane vesicles, and (iii) number of ouabain-binding sites and by similar Kd values for ouabain binding and K1/2 for ouabain inhibition of Na+,K+-ATPase as compared to the wild type. The increase in abundance of the Na+ pump is associated with a 4-fold increase in abundance of the mRNA for the alpha 1 subunit of the Na+,K+-ATPase. We could not detect mRNA for alpha 2 or alpha 3 or for the beta subunits. The increase in abundance of the A system and Na+,K+-ATPase is associated with a negligible increase in intracellular Na+ concentration. We propose that the increase in the abundance of the A system and the Na+,K+-ATPase is the result of a mutation in regulatory gene R1 that controls the A system and the Na+,K+-ATPase and is not due to a primary effect of a possible initial increase in Na+ concentration.