Protein serine / threonine phosphatase

Protein dephosphorylation is catalyzed by phospho-hydrolases called protein phosphatases. While the number of protein tyrosine kinases is roughly comparable to the number of protein tyrosine phosphatases, protein serine-threonine kinases vastly outnumber the protein serine-threonine phosphatases, of which about 25 different species are known to exist. This relative under-representation may be accounted for by the alternative diversification... 

Cohen PTW (1997) Novel protein serine/threonine phosphatases variety ist he spice of life. Trends Biochem Sci 22 245-251... 

The brain contains multiple forms of protein serine-threonine phosphatases 399... 

Protein serine-threonine phosphatases play a critical role in the control of cell function 400... 

These enzymes are more closely related, in terms of their amino acid sequences, to protein tyrosine phosphatases than to protein serine-threonine phosphatases. 

Price, N. E. and Mumby, M. C. Brain protein serine/ threonine phosphatases. Curr. Opin. Neurobiol. 9 336-342, 1999. 

Goldberg, J., Huang, H. B., Kwon,Y. G., Greengard, P., Nairn, A. C. and Kuriyan, J. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376 745-753,1995. 

The cytotoxicities of okadaic acid as EC50 against the P388 and L1210 cell lines are 1.7 nano-molar and 17 nano-molar, respectively. Additionally, okadaic acid strongly inhibits protein serine/threonine phosphatase 1,2A,... 

Barford, D. 1996. Molecular mechanisms of the protein serine/threonine phosphatases. Tr. Biochem. Sci. 21 407 412. 

Maeda T, Tsai AY, Saito H (1993) Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae. Mol Cell Biol 13 5408-5417... 

The utility of the phenacyl group is exemplified in the C-terminal deprotection [Scheme 6.70] taken from Schmidt s synthesis of the immunosuppressive and antiviral cyclodepsipeptide Didemnin.113 Here, the phenacyl ester was reduc-tively cleaved with zinc in acetic acid. A similar transformation was used in a synthesis of the potent protein serine/threonine phosphatase inhibitor Motupor-in.lM Zinc-copper couple is an attractive alternative that can be used on a large scale [Scheme 6.71 ]J70... 

Welihinda, A.A., Tirasophon, W., Green, S.R. and Kaufman, R.J. (1998) Protein serine/threonine phosphatase Ptc2p negatively regulates the unfolded-protein response by dephosphorylating Irelp kinase. Mol. Cell Biol. 18, 1967-1977. 

Phosphatases hydrolyze phosphate groups from phosphopro-teins, thereby reversing the action of protein kinases. Two classes of protein phosphatases exist with distinct structures, substrate specificities, and mechanisms protein serine/threonine phosphatases and protein tyrosine phosphatases. A few dualspecificity phosphatases also are known that are similar in structure to protein tyrosine phosphatases. 

Cohen PTW. Novel protein serine/threonine phosphatases variety is the ice of life Trends Biochem Sd 1997 22 245-51... 

Skinner J, Sinclair C, Romeo C, Armstrong D, Chaiboimeau H, Rossie S. Purificatiem of a fatty add-stimulated protein-serine threonine phosphatase from bovine brain and its idemificatiem as a homolc of protein... 

Chen J, Martin BL, Brautigan DL (1992) Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Sdence 257 1261-1264... 

McConnell JL, Wadzinski BE (2009) Targeting protein serine/threonine phosphatases for drug development. Mol Pharmacol 75 1249-1261... 

The substrates of phosphoprotein phosphatases range from simple phosphopeptides to phosphorylated enzymes involved in many biological processes. Based on substrate specificity and sequence homology, these enzymes fall into two large families, the PTPs and the protein serine/threonine phosphatases (PPs). As their name implies, the PPs dephosphorylate pSer and phosphothreonine (pThr) residues. These enzymes have binuclear metal centers and catalyze a phosphoryl transfer from the substrate directiy to water. The PPs are distinguished from the PTPs, which do not contain metal ions and dephosphorylate phosphotyrosine (pTyr) residues through a phosphoenzyme intermediate. 

Historically, the protein phosphatases were classified into two groups according to their substrate specificity tyrosine phosphatases and serine/threonine protein phosphatases. The latter are metalloenzymes we will refer to these as metallophospha-tases, a superfamily of enzymes that includes the serine/threonine protein phosphatases, purple acid phosphatases, and other enzymes capable of phosphoryl group transfer reactions such as bacteriophage A protein phosphatase [17, 18]. 

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