PTPases phosphatases

Intracellular and extracellular ROS activate tyrosine and serine-threonine kinases (i.e., the MAPK family members). Following TNF-a, TGF-f5 or EGF stimulation, intracellular ROS are generated which stimulate various signaling pathways [73], Tyrosine kinase receptors (e.g., EGF, PDGF and TGF-a) may be activated by ROS directly via protein sulfhydryl group modifications, or inhibition of phosphotyrosine phosphatases (PTPases) and subsequent receptor activation. The latter is possible as PTPases contain a redox-sensitive cysteine at their active site [78], and oxidation of protein sulfhydryl groups results in the inactivation of PTPases. 

Workers at Ontogen [82,83] reported the use of the OntoBLOCK system which utilizes a Tecan robot. They have implemented this technology for solid-phase synthesis to generate over 50 000 compounds corresponding to libraries of pyrroles, phosphonates, phosphinates, lactams, imidazoles, hydantoin imides and thioimides, oxazoles, and b-lac-tams. These libraries have resulted in potent and selective inhibitors of iNOS, PTPases and cdc25 phosphatase and compounds that reverse the P-glycoprotein (Pgp)-based multiple drug resistance (MDR) phenomenon in cellular assays and in animal models [98],... 

PTPases, P-Tyr phosphatases PUVA therapy, psoralen with ultraviolet A light therapy PYK, pyruvate kinase... 

PTEN, phosphatase and tensin homolog PTPase, phosphotyrosine phosphatase PYY, peptide YY... 

PAO of natural isotopic composition has been employed in the biosynthesis of [ P]ppl5, involving P. Subsequent use of [ P]ppl5 in bioexperiments facilitated the isolation of two (membrane) protein tyrosine phosphatases (PTPases), and permitted one to establish that more than 90% of the ppl5 dephosphorylating activity is membrane associated. The P lost from [ P]ppl5 during the bioreaction has been quantitatively recovered as Pj. 

The PTPases share the signature motif (H/V)C(X)5R(S/T). This motif is also found in the low-molecular-weight PTPases, as well as in the VH 1-like dual-specific phosphatases, so-called because they dephosphorylate phosphotyrosine as well as phospho-Ser/Thr residues.129,149 These three groups of phosphatases have little sequence similarity other than the signature motif and the placement of the essential Cys and Arg residues in the active site. 

The X-ray structures of a number of PTPases have been reported, including the catalytic domains of PTP1B complexed with tungstate150 and of Yop51 from Yersinia (residues 163-468)151 with and without complexed tungstate. The structure of the human dual-specific phosphatase VHR (Vaccina HI-related) has also been determined,152 as well as those of several low-molecular-weight PTPases, including... 

PTPase Phosphotyrosine phosphatase/protein tyrosine phosphatase ROS Reactive oxygen species... 

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