title: N-myc downregulated gene 1 is a phosphorylated protein in mast cells.
abstract: We previously demonstrated that the in vitro maturation of mouse immature bone marrow-derived mast cells into a mature connective tissue mast cell-like phenotype is accompanied by a marked induction of N-myc downregulated gene (NDRG) 1, a cytosolic protein with unknown function. Here we show that NDRG1 undergoes phosphorylation in mast cells. Recombinant NDRG1 was phosphorylated by calmodulin kinase-II, protein kinase (PK) A and PKC in vitro. Deletion of the C-terminal tandem repeats of NDRG1 resulted in increased phosphorylation by PKA and PKC, but not by calmodulin kinase-II. Furthermore, NDRG1 was phosphorylated on serine and threonine residues in mast cells, a process that was accelerated transiently following cell activation. Pharmacologic studies using kinase-specific inhibitors demonstrated that this NDRG1 phosphorylation in mast cells depended on calmodulin kinase-II and PKA, but not PKC. Collectively, our results indicate that NDRG1 is a multiphosphorylated protein in mast cells, and that the kinetics of increased NDRG1 phosphorylation parallels signaling events leading to exocytosis.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sugiki
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.forename: Rei
authors.initials: R
authors.lastname: Kikuchi-Yanoshita
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016259:Genes, myc; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein