Regulation of polyamine-responsive protein kinase by certain highly specific polyamines and charged carbohydrates.

Polyamine-responsive protein kinase, a cyclic nucleotide-independent protein kinase from the cytosol of Morris hepatoma 3924A, was stimulated 8-9 fold by several different polymers of polylysine, polyornithine and random copolymers of lysine-alanine; spermidine, spermine, and mixtures of spermine and spermidine stimulated 2, 3, and 5 fold, respectively. The protein kinase was not stimulated by poly-carboxybenzyl-lysine, random copolymer of lysine-tyrosine, polyhistidine, polymethionine, polyglutamic acid, polyaspartic acid, dipeptide (Lys-Lys), lysine, ornithine, and putresine. The polyamine stimulation of the protein kinase was prevented by certain specific charged carbohydrates: heparin, chondroitin sulfates A, B, and C, dextran sulfate and hyaluronic acid. It was not prevented by noncharged carbohydrates: dextran, glycogen, starch, sucrose, etc; or by sulfate salts: ammonium sulfate, potassium sulfate, sodium thiosulfate, etc. The inhibition was reversed by increased polylysine. Heparin was non-competitive inhibitor of Mg2+-ATP. It would appear that this enzyme is regulated by certain highly specific molecules with certain sizes and charges; plus charge is stimulatory, negative charge prevents the stimulation.