Disease relevance of Acp1

• The amino acids involved in transition-state stabilization for cysteinylphosphate hydrolysis were confirmed by the x-ray structure of the Yersinia PTPase complexed with vanadate, a transition-state mimic that binds covalently to the active-site cysteine [1].
• Engineering site-specific amino acid substitutions into the protein-tyrosine phosphatase (PTPase) PTP1 and the dual-specific vaccinia H1-related phosphatase (VHR), has kinetically isolated the two chemical steps of the reaction and provided a rare opportunity for examining transition states and directly observing the phosphoenzyme intermediate [1].
• To test the hypothesis that the transmembrane PTPase LAR can modulate insulin receptor signaling in vivo, antisense RNA expression was used to specifically suppress LAR protein levels by 63% in the rat hepatoma cell line, McA-RH7777 [2].
• Many protein-tyrosine phosphatases (PTPases) have now been identified, but little is known about PTPase expression and regulation in vascular tissue and in vascular disease [3].
• In contrast to the glomerular lesion, PTPase mRNA expression was not induced in experimental tubulointerstitial nephritis [4].

Psychiatry related information on Acp1

• Phosphotyrosine phosphatase (PTPase) activity and its regulation by overnight food deprivation were studied in Psammomys obesus (sand rat), a gerbil model of insulin resistance and nutritionally induced diabetes mellitus [5].

High impact information on Acp1

• Our results indicate that alloxan diabetes in the rat is associated with an increase in the activity of a large, membrane-associated PTPase which accounts for only a small proportion of insulin receptor tyrosine dephosphorylation [6].
• Nonetheless, increased activity of this PTPase may oppose tyrosine kinase-mediated insulin signal transmission, thus contributing to insulin resistance [6].
• Hepatic PTPase activity was measured using two artificial substrates phosphorylated on tyrosine: reduced, carboxyamidomethylated, and maleylated lysozyme (P-Tyr-RCML) and myelin basic protein (P-Tyr-MBP), as well as an autophosphorylated 48-kD insulin receptor tyrosine kinase domain (P-Tyr-IRKD) [6].
• Rats that were made alloxan diabetic exhibited a significant increase in hepatic membrane (detergent-soluble) PTPase activity measured with P-Tyr-MBP, without a change in activity measured with P-Tyr-RCML or the P-Tyr-IRKD [6].
• Phosphotyrosine phosphatase (PTPase) activity in rat liver was measured using a phosphopeptide substrate containing sequence identity to the major site of insulin receptor autophosphorylation [7].

Chemical compound and disease context of Acp1

• I demonstrate here that both the Yersinia PTPase and rat PTP1 can dephosphorylate alkyl phosphates such as flavin mononucleotide, pyridoxal 5'-phosphate, D-glucose 6-phosphate, DL-alpha-glycerophosphate, O-phospho-L-serine, and O-phospho-L-threonine [8].
• The dephosphorylation of p-nitrophenyl phosphate by Yersinia protein-tyrosine phosphatase (PTPase) and by the rat PTP1 has been examined by measurement of heavy-atom isotope effects at the nonbridge oxygen atoms [18(V/K)nonbridge], at the bridging oxygen atom [18(V/K)bridge], and the nitrogen atom in the leaving group 15(V/K) [9].
• The recombinant protein of the cloned cDNA expressed in Escherichia coli was shown to possess PTPase activity using myelin basic protein, tyrosine phosphorylated by p43v-abl tyrosine kinase, as a substrate [10].
• We studied the effect of the 3,4-dihydroxy analogue of dephostatin (3,4-dephostatin), an inhibitor of protein-tyrosine phosphatase (PTPase), on the differentiation of rat pheochromocytoma PC12 cells [11].

Biological context of Acp1

• Since tyrosine phosphorylation plays a central role in the cellular action of insulin receptor, an increase in PTPase activity may be an important factor in the altered insulin action associated with these diabetic states [7].
• Site-directed mutagenesis of a putative Ets binding site located within this 15-bp sequence, reduced PTPase, neuregulin, and Ras-dependent regulation [12].
• However, the DNA regulatory elements and the binding proteins that mediate PTPase and neuregulin-dependent gene expression remain unknown [12].
• Using polymerase chain reaction with degenerate primers and a neonatal rat cortex cDNA library, we have identified a number of putative PTPase domains expressed in brain [13].
• The potential importance of the novel change in activity of PTPase I in the regulation of insulin-receptor signal transduction is discussed [14].

Anatomical context of Acp1

• The abundance of LMW-PTP in nerve endings as well as in the cytosol suggests that this enzyme plays an important role in synaptic function [15].
• The distribution of low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) in subcellular fractions of rat brain tissue was investigated by immunoblotting analysis using anti-LMW-PTP antibody [15].
• Abundance of low molecular weight phosphotyrosine protein phosphatase in the nerve-ending fraction in the brain [15].
• Incubation with the PTPase inhibitor bpV(phen) inhibited tER assembly coincident with the enhanced tyrosine phosphorylation of endogenous p97 and its release from membranes [16].
• Purification of the endogenous tyrosine kinase activity from low-density microsomes led to the identification of JAK-2, whereas PTPH1 was identified as the relevant PTPase [16].

Associations of Acp1 with chemical compounds

• Nerve ending LMW-PTP was effectively solubilized by 1% Triton X-100 or 1% deoxycholate, though the enzyme was solubilized by thorough sonication [15].
• In rats made insulin-deficient diabetic by streptozotocin treatment (STZ), cytosolic PTPase activity increased to 180% of the control values after 2 d of diabetes and remained elevated at 30 d (P less than 0.02) [7].
• High doses of molybdate, a potent PTPase inhibitor, block the phosphorylation of p42MAPK and entry into the cell cycle [17].
• These results, for the first time, directly identify the highly reactive cysteine residue at the active site of a PTPase and highlight the ability of this residue to participate as a nucleophile in the hydrolysis of phosphate from tyrosine [18].
• Iodoacetate reacts only with the first domain of this double domain PTPase [18].

Enzymatic interactions of Acp1

• Additionally, protein tyrosine phosphatase (PTPase) activities towards immobilized phosphorylated insulin receptor or phosphorylated IRS-1 of membrane (MF) and cytosolic fractions (CF) of these tissues were measured [19].

Regulatory relationships of Acp1

• Because Stat factors are known to be inactivated by protein tyrosine phosphatases (PTPase), we showed that a PTPase is able to eliminate the DNA binding of hepatic Stat3.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
• PTPase activity was regulated by both acute and chronic insulin and IGF-I treatment [21].
• In conclusion, inhibition of PTPase activity by pV stimulates basal and inhibits arginine-induced glucagon release [22].
• We conclude that pancreatic acinar membranes possess a low-molecular-mass PTPase which is stimulated by somatostatin analogs at concentrations involving activation of membrane somatostatin receptors [23].

Other interactions of Acp1

• A novel cytoplasmic protein-tyrosine phosphatase (PTPase) designated PTP20 was isolated from a PC12 cDNA library and shown to positively regulate the differentiation process in PC12 cells [24].
• Previously we found that rat mesangial cells express 3CH134/CL100 protein-tyrosine phosphatase (PTPase) in response to reactive oxygen intermediates (ROIs), and we now extend these studies to glomerulonephritis (GN), where ROI have been demonstrated to play a role [4].
• These studies indicate that three PTPases with markedly divergent structures have the catalytic potential to dephosphorylate both insulin and EGF receptors in intact cells and that redundant PTPase activity may occur in vivo [25].
• Overexpression of the PTPLP decreased the basal PTPase activity of COS-7 cells for Raytide [26].
• To identify PTPases that are recruited to the activated TrkA receptor, we used an in-gel PTPase assay to examine the presence of PTPases in TrkA immunoprecipitates [27].

Analytical, diagnostic and therapeutic context of Acp1

• The PTPase active with P-Tyr-MBP behaved as a high molecular weight peak during gel filtration chromatography [6].
• An antibody raised against PTPase 1B, the prototype of this class of PTPases, did not react with PTPase I in Western blots [14].
• In situ hybridization suggested that mesangial and some infiltrating cells were the major glomerular cell sources of the PTPase mRNA [4].
• Further purification by HPLC on DEAE revealed two peaks of PTPase activity at 120 mM and 180 mM NaCl [23].
• Moreover, depletion of solubilized membrane preparations from G-proteins by lectin affinity chromatography does not alter Ang II stimulation of the measured PTPase activity [28].

References