The catalytic subunit of cAMP-dependent protein kinase contains two stable phosphorylation sites, Thr-197 and Ser-338 (Shoji, S., Titani, K., Demaille, J. G., and Fischer, E. H. (1979) J. Biol. Chem. 254, 6211-6214). Thr-197 is very resistant to dephosphorylation and thus cannot typically be autophosphorylated in vitro once the stable subunit is formed. Ser-338 is slowly dephosphorylated and ca...

Recent investigations have suggested that common genetic polymorphisms in BRCA1-associated C-terminal helicase 1 (BACH1) are important in the development of breast cancer. However, individually published studies and previous meta-analyses have demonstrated inconclusive results. The aim of this meta-analysis was to derive a more precise estimation of the correlation between a common polymorphism...

Osmotic shock induced transient stabilization of p53, possibly due to increased degradation of Mdm2. Stabilized p53 was activated by p38(MAPK), resulting in G(1) arrest through induction of p21(WAF1). Among the postulated phosphorylation sites involved in p53 stabilization or activation (Ser(15), Ser(20), Ser(33), and Ser(46)), only Ser(33) was phosphorylated. Furthermore, interaction of p53 wi...

Although glial cell-line derived neurotrophic factor (GDNF) acts as a potent survival factor for dopaminergic neurons, it is not known whether GDNF can directly alter dopamine synthesis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for dopamine biosynthesis, and its activity is regulated by phosphorylation on three seryl residues: Ser-19, Ser-31, and Ser-40. Using a TH-expressing human...

The ataxia telangiectasia mutated- and rad3-related kinase (ATR)/Chk1 pathway is a sentinel of cell cycle progression. On the other hand, the Ras/mitogen-activated protein kinase/90-kDa ribosomal S6 kinase (p90 RSK) pathway is a central node in cell signaling downstream of growth factors. These pathways are closely correlated in cell proliferation, but their interaction is largely unknown. Here...

Selenoproteins are proteins carrying the rare amino acid Sec (selenocysteine). Full expression of selenoproteins requires modification of tRNA([Ser]Sec), including N(6)-isopentenylation of base A(37). We show that Trit1 is a dimethylallyl:tRNA([Ser]Sec) transferase. Knockdown of Trit1 reduces expression of selenoproteins. Incubation of in vitro transcribed tRNA[Ser]Sec with recombinant Trit1 tr...

FKHR is a member of the FOXO subfamily of Forkhead transcription factors, which are important targets for insulin and growth factor signaling. FKHR contains three predicted protein kinase B phosphorylation sites (Thr-24, Ser-256, and Ser-319) that are conserved in other FOXO proteins. We have reported that phosphorylation of Ser-256 is critical for the ability of insulin and insulin-like growth...

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP; also known as gastric inhibitory polypeptide) are incretin hormones that reduce postprandial glycemic excursions via enhancing insulin release but are rapidly inactivated by enzymatic N-terminal truncation. As such, efforts have been made to improve their plasma stability by synthetic modification or by inhib...