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Evaluation of in vitro properties of predicted kinases that phosphorylate serine residues within nuclear localization signal 1 of high mobility group box 1
Author(s) -
Taira Junichi,
Higashimoto Yuichiro
Publication year - 2014
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2630
Subject(s) - phosphorylation , kinase , protein serine threonine kinases , nuclear localization sequence , nuclear transport , serine , hmgb1 , subcellular localization , microbiology and biotechnology , protein phosphorylation , chemistry , nuclear export signal , cytosol , protein kinase a , biochemistry , biology , cytoplasm , cell nucleus , enzyme , receptor
Phosphorylation of high mobility group box 1 (HMGB1) is involved in the subcellular translocation of this protein and its subsequent secretion. Two nuclear localization signals (NLSs), NLS1 and NLS2, in this protein regulate its nucleocytoplasmic relocation, and phosphorylation of both NLSs strongly promotes HMGB1 mobilization. However, the phosphorylation properties of serine residues in NLS1 and the kinases involved are not well known. In the present study, we predicted kinases that phosphorylate serine residues in NLS1 and performed an in vitro kinase assay utilizing NLS1‐derived phosphopeptides. Among the predicted kinases, protein kinase C phosphorylated Ser 46 of HMGB1‐derived peptides, and a mutagenesis experiment confirmed that phosphorylation at this site could induce the translocation of the N‐terminal region of NLS1‐containing HMGB1 into the cytosol. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.