title: Effects of taurine and taurine analogues on the phosphorylation of a 44 kDa protein present in a mitochondrial subfraction of the rat heart: partial characterization of the 44 kDa phosphoprotein.
abstract: Recent studies suggest that taurine (2-aminoethanesulfonic acid) is involved in the regulation of protein phosphorylation in excitable tissues such as the retina, brain and heart. In order to determine the structural requirements for the effect of taurine on the phosphorylation of a 44 kDa protein(s), a series of taurine analogues were tested in an in vitro assay using a subcellular mitochondrial fraction of rat heart. Inhibitors of the phosphorylation of the 44 kDa protein include taurine and close structural analogues of taurine such as aminoethylhydrogen sulfate and alpha-sulfo-beta-alanine. Secondary amines with the taurine structure partially locked into a saturated 5-membered ring such as (+/-)piperidine-3-sulfonic acid and 1,2,3,4-tetrahydroquinoline-8-sulfonic acid also possess inhibitory activity. Sulfone analogues of taurine such as 2-aminoethylmethylsulfone, a non-restricted taurine analogue with maximal conformational flexibility about its amino and sulfone moieties, and (+/-)3-aminotetrahydrothiopyran-1,1-dioxide, an analogue containing the sulfone moiety in a six-membered ring structure, were found to be more potent inhibitors of phosphorylation than taurine despite the fact that the sulfone moiety is neither an isosteric nor isoelectronic substitution for the sulfonic acid moiety. The results of this study indicate that the inhibition of the phosphorylation of the 44 kDa protein in a rat heart mitochondrial fraction is relatively specific for the taurine structure. Two analogues of taurine with unsaturated rings containing a primary sulfonic acid and a secondary amine, pyridine-3-sulfonic acid and quinoline-8-sulfonic acid, were observed to be stimulators of the phosphorylation of the 44 kDa protein. In addition, 2-aminobenzenesulfonic acid also stimulated phosphorylation. Phase separation experiments with Triton X-114 suggest that the 44 kDa phosphoprotein is a soluble protein and not an integral membrane protein of the mitochondria. Phosphate incorporation into specific amino acids was determined by two-dimensional electrophoresis on celluloses plates and was found exclusively in the serine residues.
authors.affiliation: Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430.
authors.forename: J B
authors.initials: JB
authors.lastname: Lombardini
mesh_terms: D000818:Animals; D003902:Detergents; D006868:Hydrolysis; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D017830:Octoxynol; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation; D011092:Polyethylene Glycols; D051381:Rats; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D003902:Detergents; D010750:Phosphoproteins; D013654:Taurine; D011092:Polyethylene Glycols; D017830:Octoxynol; C010615:Nonidet P-40