RRC ID 41629
Author Matsuoka K, Kiyokawa N, Taguchi T, Matsui J, Suzuki T, Mimori K, Nakajima H, Takenouchi H, Weiran T, Katagiri YU, Fujimoto J.
Title Rum1, an inhibitor of cyclin-dependent kinase in fission yeast, is negatively regulated by mitogen-activated protein kinase-mediated phosphorylation at Ser and Thr residues.
Journal Eur J Biochem
Abstract The p25(rum1) is an inhibitor of Cdc2 kinase expressed in fission yeast and plays an important role in cell-cycle control. As its amino-acid sequence suggests that p25(rum1) has putative phosphorylation sites for mitogen-activated protein kinase (MAPK), we investigated the ability of MAPK to phosphorylate p25(rum1). Direct in vitro kinase assay using GST-fusion proteins of wild-type as well as various mutants of p25(rum1) demonstrated that MAPK phosphorylates the N-terminal portion of p25(rum1) and residues Thr13 and Ser19 are major phosphorylation sites for MAPK. In addition, phosphorylation of p25(rum1) by MAPK revealed markedly reduced Cdc2 kinase inhibitor ability of the protein. Together with the fact that replacement of both Thr13 and Ser19 with Glu, which mimics the phosphorylated state of these residues, also significantly reduces the activity of p25(rum1) as a Cdc2 inhibitor, it was suggested that the phosphorylation of Thr13 and Ser19 negatively regulates the function of p25(rum1). Further evidence indicates that phosphorylation of Thr13 and Ser19 may retain a negative effect on the function of p25(rum1) even in vivo. Therefore, MAPK may regulate the function of p25(rum1) via phosphorylation of its Thr and Ser residues and thus participate in cell cycle control in fission yeast.
Volume 269(14)
Pages 3511-21
Published 2002-7-1
DOI 10.1046/j.1432-1033.2002.03033.x
PII 3033
PMID 12135491
MeSH Amino Acid Substitution Animals CDC2 Protein Kinase / antagonists & inhibitors Cell Cycle Mice Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases / metabolism* Phosphorylation Phosphoserine / chemistry Phosphothreonine / chemistry Protein Processing, Post-Translational* Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / antagonists & inhibitors Schizosaccharomyces pombe Proteins / metabolism* Starfish
Times Cited 9
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells