Regulation of amino acid transport activity and growth rate of animal cells in culture.

Balb/3T3 mouse cells grown in cell culture contain the A and L systems for neutral amino acid transport. L-Alanine was used as a test amino acid for the A system and L-leucine for the L system. Transport activities for both transport systems are altered as the growth conditions for the cells are altered. When cell growth was arrested by allowing cells to approach confluency, or by the removal of serum or by the addition of protein synthesis inhibitors, System A transport activity decreased and System L activity increased significantly. The content of the cellular amino acids increased 2- to 3-fold whenever cell growth was arrested by the conditions stated above. Increased cellular amino acids, therefore, are associated with decreased transport activity of System A and increased activity of System L. Altering cellular amino acids by loading or depleting the cells produced the predicted responses for the rapidly exchanging L-system but System A was less responsive. It is possible that regulatory mechanisms operate for the A system other than the direct action of alterations in cellular amino acid levels. The implications of the amino acid transport activity changes observed here on various studies on the role of transport in cell growth regulation and malignant transformation are discussed.