Phosphatase tyrosine

Zhang, Z.-Y., Dixon, J. E. Active site labeling of the yersinia protein tyrosine phosphatase The determination of the pKa of active site cysteine and the function of the conserved histidine 402. Biochem. 32 (1993) 9340-9345. 

Figure 4 Schematic diagram of the first step of the reaction catalyzed hy bovine protein tyrosine phosphatase (BPTP) formation of the cysteinyl phosophate intermediate.

Hydrogen peroxide (H202) exhibits insulin-like activity in isolated cells. Like that of vanadate, this effect is thought to be mediated by inhibition of protein-tyrosine phosphatases. 

STAT binding site in the promoter region of cytokine-responsive genes. It is nonameric palindrome with relaxed sequence specificity.) sites, to regulate gene expression. Tyrosine phosphatases located in the nucleus then dephosphorylate STAT molecules (Fig. 1). 

Protein Phosphatases. Figure 3 Classification of protein tyrosine phosphatases. See text for details. Common names for selected PTPs are used according to Ref. [2]. 

Numerous protein phosphatases are targeted to their substrates and regulators through the interaction with specific scaffolding proteins. Some of these anchoring proteins bind both, kinases and phosphatases. This applies to ser/thr protein phosphatases as well as to tyrosine phosphatases. 

Tonks NK (2006) Protein tyrosine phosphatases from genes, to function, to disease. Nat Rev Mol Cell Biol 7 833-846... 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

In contrast to tyrosine kinases, Tyrosine phosphatases (PTPs) are enzymes which act on phosphorylated proteins and catalyze the transfer of a phosphate group from a tyrosine residue to a water molecule, generating orthophosphates in a process which is referred to as dephosphorylation. PTPs are involved in many cellular signal transduction pathways. 

When considering the role of phosphorylation in the regulation of the HS response, it is indeed curious that oxidative stress and heat induce a protein tyrosine phosphatase at the transcriptional level (Keyse and Emslie, 1992). Whether this phosphatase has any role in the regulation of HSF phosphorylation is not known, but it does indicate that both transcriptional and translational regulation of signaling... 

Keyse, S.M. Emslie, E.A. (1992). Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. Nature 359, 644-647. 

IL-10 inhibits CD28 and ICOS costimulations of T 127 cells via Src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Chn Immunol 2007 120 76-83. 

Perret D, Shields M, Saxon A, Kehry MR A mouse Fey Fee protein that inhibits mast cells through activation of FcyRIIB, SH2 domain-containing inositol SS phosphatase 1, and SH2 domain-containing protein tyrosine phosphatases. J Allergy Chn Immunol 2008 121 441-447. 

AmpC P-Lactamase Phosphodiesterase 4 Protein Tyrosine Phosphatase IB... 

Protein tyrosine phosphatase IB (PTP1B) inhibitor. IC5o = 4.1 pM... 

Doman TN, McGovern SL, Witherbee BJ, Kasten TP, Kurumbail R, Stallings WC, Connolly DT, Shoichet BK. Molecular docking and high throughput screening for novel inhibitors of protein tyrosine phosphatase IB. J Med Chem 2002 45 2213-21. 

Walton KM, Dixon JE Protein tyrosine phosphatases. Annu Rev Biochem 1993 62 101. 

GAO Y H and YAMAGUCHI M (2000) Suppressive effect of genistein on rat bone osteoclasts Involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5, 261-7. 

JOHNSON T o, ERMOLIEFF J and JiROUSEK M R (2002) Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Discov. 1 (9) 696-709. 

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