title: CoA Synthase is phosphorylated on tyrosines in mammalian cells, interacts with and is dephosphorylated by Shp2PTP.
abstract: CoA Synthase (CoASy, 4'-phosphopantetheine adenylyltransferase/dephospho-CoA kinase) mediates two final stages of de novo coenzyme A (CoA) biosynthesis in higher eukaryotes. Unfortunately very little is known about regulation of this important metabolic pathway. In this study, we demonstrate that CoASy interacts in vitro with Src homology-2 (SH2) domains of a number of signaling proteins, including Src homology-2 domains containing protein tyrosine phosphatase (Shp2PTP). Complexes between CoASy and Shp2PTP exist in vivo in mammalian cells and this interaction is regulated in a growth-factor-dependent manner. We have also demonstrated that endogenous CoASy is phosphorylated on tyrosine residues in vivo, and that cytoplasmic protein tyrosine kinases can mediate this phosphorylation in vitro and in vivo. Importantly, Shp2PTP-mediated CoASy in vitro dephosphorylation leads to an increase in CoASy enzymatic phosphopantetheine adenylyltransferase (PPAT) activity. We therefore argue that CoASy is a novel potential substrate of Shp2PTP and phosphorylation of CoASy at tyrosine residue(s) could represent unrecognized before mechanism of modulation intracellular CoA level in response to hormonal and (or) other extracellular stimuli.
authors.affiliation: Department of Cell Signaling, Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Zabolotnogo Street, 03680 Kyiv, Ukraine.
authors.forename: Oksana
authors.initials: O
authors.lastname: Breus
authors.forename: Ganna
authors.initials: G
authors.lastname: Panasyuk
authors.forename: Ivan T
authors.initials: IT
authors.lastname: Gout
authors.forename: Valeriy
authors.initials: V
authors.lastname: Filonenko
authors.forename: Ivan
authors.initials: I
authors.lastname: Nemazanyy
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D010766:Phosphorylation; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D014443:Tyrosine; D014166:Transferases; C509687:COASY protein, human; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases