CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein Journal Article
| Authors: | Cho, W. H.; Lee, Y. J.; Kong, S. I.; Hurwitz, J.; Lee, J. K. |
| Article Title: | CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein |
| Abstract: | Cdc7 is an essential kinase required for the initiation of eukaryotic DNA replication. Previous studies in many species showed that the minichromosome maintenance complex is a major physiological target of this kinase. In this study, we have mapped the sites in human Mcm2 protein that are phosphorylated by Cdc7. The in vitro phosphorylation of several Mcm2 truncated proteins and peptides revealed that Mcm2 contains two major (5S and 53S) and at least three minor phosphorylation sites (4S, 7S, and 59T) located at the N-terminal region. Alanine substitution experiments with Mcm2 peptides showed that the phosphorylation of 5S and 53S by Cdc7 required the presence of an acidic amino acid adjacent to a serine residue. Furthermore, although Cdc7 was unable to phosphorylate a Mcm2 peptide (spanning amino acids 19-30 and containing 26S and 27S), it phosphorylated 26S efficiently when this peptide contained a chemically synthesized phospho-27S modification. Hence, additional Cdc7 phosphorylation sites could be generated in Mcm2 by its prior phosphorylation by a cyclin-dependent kinase. This finding may explain why the sequential action of cyclin-dependent and Cdc7 kinases is essential for the initiation of DNA replication. © 2006 by The National Academy of Sciences of the USA. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; nonhuman; dna replication; cell cycle protein; animals; cell cycle proteins; mice; amino acid substitution; serine; protein targeting; in vitro study; tyrosine; phosphorylation; nuclear proteins; amino acid sequence; molecular sequence data; amino terminal sequence; recombinant fusion proteins; eukaryota; protein-serine-threonine kinases; amino acid; alanine; phosphotransferase; peptide synthesis; eukaryote; protein modification; acidity; replication; minichromosome maintenance protein 2; cell cycle protein 7; origin activation; prereplicative complex; minichromosome; amino acids, acidic |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 103 |
| Issue: | 31 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2006-08-01 |
| Start Page: | 11521 |
| End Page: | 11526 |
| Language: | English |
| DOI: | 10.1073/pnas.0604990103 |
| PUBMED: | 16864800 |
| PROVIDER: | scopus |
| PMCID: | PMC1544202 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 29" - "Export Date: 4 June 2012" - "CODEN: PNASA" - "Source: Scopus" |
