Disease relevance of ACP1

• In this paper we describe the construction of five mutants of a bovine liver low M(r) phosphotyrosine protein phosphatase (PTPase) expressed as a fusion protein with the maltose binding protein in E. coli [1].
• Since all members of the PTPase family have the same reaction mechanism and possess a conserved active site motif that contains an essential cysteine residue, the findings on low M(r) and Yersinia PTPases are potentially interesting for all PTPases, an enzyme class that is involved in a number of important biological processes [2].

High impact information on ACP1

• The structure of the low-molecular-weight PTPase supports a reaction mechanism involving the conserved Cys 12 as an attacking nucleophile in an in-line associative mechanism [3].
• The second PTPase like domains do not have detectable catalytic activity using a variety of substrates, but sequences within the second domains influence substrate specificity [4].
• That suramin is a high affinity PTPase inhibitor is consistent with the observation that suramin treatment of cancer cell lines leads to an increase in tyrosine phosphorylation of several cellular proteins [5].
• Suramin is a reversible and competitive PTPase inhibitor with Kis values in the low microM range, whereas the Kis for the dual specificity phosphatase VHR is at least 10-fold higher [5].
• The low M(r) phosphotyrosine protein phosphatase (PTPase) and Yersinia enterocolitica PTPase are inactivated by nitric oxide-generating compounds [2].

Biological context of ACP1

• The complete amino acid sequence of the low molecular weight cytosolic acid phosphatase [6].
• The location and enzymatic significance of the residues in the characteristic low molecular weight PTPase active site motif, including the essential arginine (Arg 18) and nucleophilic cysteine (Cys 12), are described [7].
• In this study the mechanism of benzoyl-phosphate hydrolysis was studied by means of non-mutated and mutated PTPase fusion proteins [8].
• Adenosine and/or homocysteine causes endothelial cell apoptosis, a mechanism requiring protein tyrosine phosphatase (PTPase) activity [9].
• We used NIH/3T3 fibroblasts, both normal and transformed by the oncogenes v-erbB, v-src, and v-raf: a synthetic gene coding for PTPase was transfected into, and overexpressed in, normal and transformed NIH/3T3 cells with resulting inhibition of cell growth [10].

Anatomical context of ACP1

• The relationship between the ACP1 gene product, an 18kDa acid phosphatase (E.C. 3.1.3.2) postulated to function as a protein tyrosyl phosphatase, and the cellular flavin mononucleotide (FMN) phosphatase has been examined in vitro and by using cultured Chinese hamster ovary (CHO) cells [11].
• We conclude that this novel PTPase is active on cell type-specific signalling substrates that control normal and transformed fibroblast proliferation [10].
• The PTPase inhibitor sodium orthovanadate did not prevent endothelial cell retraction or FAK, paxillin, or vinculin redistribution [9].
• Focal adhesion contact disruption induced by adenosine-homocysteine is independent of PTPase or caspase activation [9].
• Low molecular weight phosphotyrosine protein phosphatase from PC12 cells. Purification, some properties and expression during neurogenesis in vitro and in vivo [12].

Associations of ACP1 with chemical compounds

• Low-M(r) phosphotyrosine protein phosphatase (PTPase), previously known as low-M(r) acid phosphatase, catalyzes the in-vitro hydrolysis of tyrosine phosphorylated proteins, low-M(r) aryl phosphates and natural and synthetic acyl phosphates [8].
• Nitric oxide causes inactivation of the low molecular weight phosphotyrosine protein phosphatase [2].
• Low M(r) PTPase from bovine liver lost two out of eight thiol groups present in the molecule during the inactivation with sodium nitroprusside and with other NO-producing compounds [2].
• In support of this is the co-precipitation of a PTPase activity with the nicotinic acetylcholine receptor and co-chromatography of this receptor with one or the c-Src-PTPase complexes [13].
• Adenosine significantly elevated the PTPase activity in the ECs [14].

Regulatory relationships of ACP1

• Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S-adenosylhomocysteine hydrolase with MDL-28842 [14].

Analytical, diagnostic and therapeutic context of ACP1

• The role of Asp128 in the catalytic mechanism of the low Mr protein-tyrosine phosphatase (PTPase) from the fission yeast Schizosaccharomyces pombe has been investigated by a combination of site-directed mutagenesis and pre-steady-state and steady-state kinetic analysis [15].

References