Identification of protein-ribulosamine-5-phosphatase as human low-molecular-mass protein tyrosine phosphatase-A.
Ribulosamines, which are substrates for the deglycating enzyme fructosamine-3-kinase-related protein, are presumably formed intracellularly through glycation of proteins with ribose 5-phosphate followed by dephosphorylation of resulting RN5Ps (ribulosamine 5-phosphates) by a putative RN5Pase (ribulosamine-5-phosphatase). Ribose 5-phosphate is known to be a potent glycating agent and we show in the present study that it reacts approximately 10 and 80-fold more rapidly with protein than ribose and glucose respectively. We also show that tissue extracts and, most particularly, erythrocyte extracts contain a protein-RN5Pase. We have purified this enzyme from human erythrocytes to near homogeneity and shown it to correspond to LMWPTP-A [low-molecular-mass ('weight') protein tyrosine phosphatase-A]. Human recombinant LMWPTP-A displayed an RN5Pase activity that was higher than its tyrosine phosphatase activity, indicating that this phosphatase may participate in protein deglycation, a new form of protein repair.
Fortpied
Juliette
J
Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Gemayel
Rita
R
Vertommen
Didier
D
Van Schaftingen
Emile
E
D000595:Amino Acid Sequence; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D006031:Glycosylation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012267:Ribosemonophosphates / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
D011956:Receptors, Cell Surface; D012267:Ribosemonophosphates; C031626:ribose-5-phosphate; C479999:FN3KRP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D010749:Phosphoprotein Phosphatases; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; C516845:Ptpra protein, rat; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4