2-COMPONENT KINASE-LIKE ACTIVITY OF NM23 CORRELATES WITH ITS MOTILITY-SUPPRESSING ACTIVITY

Nm23 genes, which encode nucleoside diphosphate kinases, have been imp licated in suppressing tumor metastasis. The motility of human breast carcinoma cells can be suppressed by transfection with wild-type nm23- H1, but not by transfections with two nm23-H1 mutants, nm23-N1(S120G) and nm23-H1(P96S). Here we report that nm23-H1 can transfer a phosphat e from its catalytic histidine to aspartate or glutamate residues on 4 3-kDa membrane proteins, One of the 43-kDa membrane proteins was not p hosphorylated by either nm23-H1(P96S) or nm23-H1(S120G), and another w as phosphorylated much more slowly by nm23-H1(P96S) and by nm23-H1(S12 0G) than by wild-type nm23-H1. Nm23-H1 also can transfer phosphate fro m its catalytic histidine to histidines on ATP-citrate lyase and succi nic thiokinase. The rates of phosphorylation of ATP-citrate lyase by n m23-H1(S120G) and nm23-H1(P96S) were similar to that by wild-type nm23 -H1. The rate of phosphorylation of succinic thiokinase by nm23-H1(S12 0) was similar to that by mild-type nm23-H1, and the rate of phosphory lation of succinic thiokinase by nm23-H1(P96S) mas about half that by wild-type nm23-H1. Thus, the transfer of phosphate from nm23-H1 to asp artates or glutamates on other proteins appeals to correlate better wi th the suppression of motility than does the transfer to histidines.