Phosphorylation of geranyl and farnesyl pyrophosphates by Nm23 proteins/nucleoside diphosphate kinases.
The biochemical mechanism(s) by which Nm23 proteins/nucleoside diphosphate kinases suppress tumor metastasis, inhibit cell motility, and affect cellular differentiation are not known. Here we report that Nm23 proteins can phosphorylate geranyl and farnesyl pyrophosphates to give triphosphates. Wild type Nm23-H1 had higher geranyl and farnesyl pyrophosphate kinase activities than did mutants of Nm23-H1 that do not inhibit cell motility. The phosphorylation of farnesyl pyrophosphate appears to occur in vivo as cells with an elevated level of Nm23-H1 contained more farnesyl triphosphate than did control cells. To our knowledge, this is the first report that farnesyl triphosphate exists in cells. The phosphorylation of farnesyl pyrophosphate by Nm23 proteins could alter isoprenoid metabolism, and cells with an elevated level of Nm23 proteins were found to contain more farnesylated 46- and 24-kDa proteins than did control cells. The phosphorylation of geranyl and farnesyl pyrophosphates by Nm23 proteins provides a novel mechanism by which these proteins might exert their biological effects.
Wagner
P D
PD
Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. wagnerp@dc37a.nci.nih.gov
Vu
N D
ND
D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D010766:Phosphorylation; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D017368:Protein Prenylation; D051381:Rats; D012717:Sesquiterpenes; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D014157:Transcription Factors; C015234:geranyl pyrophosphate; C004808:farnesyl pyrophosphate; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins