Protein tyrosine phosphatases PTPases

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. 

MALDI-TOF-MS has been demonstrated as a useful tool in pre-steady state kinetic research by Houston et al., who combined it off-line with quench-flow methods to follow the appearance of a protein tyrosine phosphatase (PTPase) reaction intermediate.12 Houston et al. were able to measure rate constants up to 30 s 1, with k2/k3 ratios up to approximately 15. The device described in this chapter extends this technique to measure rate constants approximately 5 times greater, with k2/k3 ratios approximately twice previously measurable values. MALDI-TOF-MS is typically conducted on a centimeter-scale conducting plate the digital microfluidic system employed is a square plate approximately 2 cm on each side, with 16 experimental units per chip, which can be placed directly inside a standard MALDI-TOF-MS plate that has been machined appropriately. By grounding the exposed wires on the otherwise insulated chip, charging is negligible. 

Protein tyrosine phosphatases (PTPases) are an important class of enzymes for the regulation of signal transduction pathways that control a number of cellular processes including cell growth and differentiation. The phosphorylation of tyrosyl protein residues has been shown to be one of the key events involved in intracellular signaling for selective gene activation. The PTPases have been shown to work in concert with... 

Protein tyrosine phosphatase (PTPase) and PTPase inhibitors... 

When feeding has finished, insulin secretion stops and insulin signal transduction within the cell must be terminated. Dephosphorylation of the insulin receptor by protein tyrosine phosphatase (PTPase) occurs, which inactivates the insulin receptor and insulin signalling ceases. However, there is evidence that some diabetic patients have a form of PTPase that is inappropriately active and opposes normal activation of the receptor by phosphorylation. Currently, there is a major research effort to develop drugs that inhibit PTPase and provide a new treatment for type 2 diabetes. 

Two protein tyrosine phosphatases (PTPases) have been studied with hybrid potentials — the catalytic domain of human PTPIB [89] and the bovine PTPase (BPTP) [90]. These proteins have similar active centers and there is an invariant catalytic cysteine amino acid residue. Hillier et al characterized the transition state for the phosphate hydrolysis by PTPIB (with a dianion phosphate) using a PM3/MM potential but keeping the protein matrix and some of the QM atoms fixed. They found a dissociative mechanism in which the cleavage of the P-0 bond occurred before the formation of the S-P bond. The breaking of the P-O bond was determined to be the rate limiting step in agreement with kinetic... 

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