PMID- 10561590 OWN - NLM STAT- MEDLINE DCOM- 20021203 LR - 20190620 IS - 0014-2956 (Print) IS - 0014-2956 (Linking) VI - 266 IP - 2 DP - 1999 Dec TI - Identification of a CK2 phosphorylation site in mdm2. PG - 493-501 AB - Mdm2 is a cellular oncoprotein the most obvious function of which is the down-regulation of the growth suppressor protein p53. It represents a highly phosphorylated protein but only little is yet known about the sites phosphorylated in vivo, the kinases that are responsible for the phosphorylation or the functional relevance of the phosphorylation status. Recently, we have shown that mdm2 is a good substrate for protein kinase CK2 at least in vitro. Computer analysis of the primary amino acid sequence of mdm2 revealed 19 putative CK2 phosphorylation sites. By using deletion mutants of mdm2 and a peptide library we identified the serine residue at position 269 which lies within a canonical CK2 consensus sequence (EGQELSDEDDE) as the most important CK2 phosphorylation site. Moreover, by using the mdm2 S269A mutant for in vitro phosphorylation assays this site was shown to be phosphorylated by CK2. Binding studies revealed that phosphorylation of mdm2 at S269 does not have any influence on the binding of p53 to mdm2. FAU - Gotz, C AU - Gotz C AD - Department of Medical Biochemistry and Molecular Biology, University of the Saarland, Homburg, Germany. bccgoe@med-rz-uni-sb.de FAU - Kartarius, S AU - Kartarius S FAU - Scholtes, P AU - Scholtes P FAU - Nastainczyk, W AU - Nastainczyk W FAU - Montenarh, M AU - Montenarh M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Biochem JT - European journal of biochemistry JID - 0107600 RN - 0 (Codon) RN - 0 (Nuclear Proteins) RN - 0 (Peptides) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) RN - EC 2.7.11.1 (Casein Kinase II) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Binding Sites MH - Blotting, Western MH - Casein Kinase II MH - Cell Line MH - Codon MH - Electrophoresis, Polyacrylamide Gel MH - Escherichia coli/metabolism MH - Humans MH - Insecta MH - Molecular Sequence Data MH - Mutation MH - *Nuclear Proteins MH - Peptides/chemistry MH - Phosphorylation MH - Plasmids/metabolism MH - Protein Binding MH - Protein Structure, Tertiary MH - Protein-Serine-Threonine Kinases/*chemistry MH - Proto-Oncogene Proteins/*chemistry/metabolism MH - Proto-Oncogene Proteins c-mdm2 MH - Recombinant Proteins/metabolism MH - Sequence Homology, Amino Acid MH - Tumor Suppressor Protein p53/metabolism EDAT- 1999/11/24 09:00 MHDA- 2002/12/04 04:00 CRDT- 1999/11/24 09:00 PHST- 1999/11/24 09:00 [pubmed] PHST- 2002/12/04 04:00 [medline] PHST- 1999/11/24 09:00 [entrez] AID - ejb882 [pii] AID - 10.1046/j.1432-1327.1999.00882.x [doi] PST - ppublish SO - Eur J Biochem. 1999 Dec;266(2):493-501. doi: 10.1046/j.1432-1327.1999.00882.x.