title: Inhibition of NF-kappaB signaling via tyrosine phosphorylation of Ymer.
abstract: Cytoplasmic zinc finger protein A20 functionally dampens inflammatory signals and apoptosis via inhibition of NF-kappaB activation. We have reported that Ymer interacts with A20 and lysine (K)-63-linked polyubiquitin chain and that Ymer inhibits NF-kappaB signaling in collaboration with A20. It has also been reported that Ymer is phosphorylated by EGF stimulation. We found that Ymer was considerably phosphorylated on tyrosine residues also via Src family kinases such as Lck. A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling. Furthermore, a soft agar colony formation assay showed that the combination of SrcY527F and YmerY217/279/304F has no ability for anchorage-independent growth, suggesting that tyrosine phosphorylation of Ymer is important for inhibition of the NF-kappaB-mediated apoptotic pathway. These findings demonstrate that Ymer is likely to be a negative regulator for the NF-kappaB signaling pathway.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kameda
authors.forename: Masashi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Miyuki
authors.initials: M
authors.lastname: Bohgaki
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Tsukiyama
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D015398:Signal Transduction; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C478972:CCDC50 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D014443:Tyrosine; D019061:src-Family Kinases