Disease relevance of Acp1

• YopH is a plasmid-encoded protein tyrosine phosphatase (PTPase) secreted by pathogenic Yersinia [1].
• Expression of the transmembrane PTPase receptor protein tyrosine phosphatase alpha (RPTP alpha) is transiently enhanced during neuronal differentiation of embryonal carcinoma (EC) and neuroblastoma cells [2].
• Herein, a distinct protein-tyrosine phosphatase (PTPase) in membrane preparations from v-Ras transformed NIH 3T3 cells was found to be activated by guanyl-5'-yl imidodiphosphate (GMPPNP) and was identified as an effector for pertussis toxin (PTx)-sensitive G-protein alpha subunits [3].
• Our results suggest that by stimulating the beta-globin and ALAS-E gene expression, PTPase plays a critical role in the induced differentiation of IW32 erythroleukemia cells [4].
• We have investigated the pattern of PTPase transcript expression during in vitro differentiation of mouse embryonal carcinoma (F9) cells [5].

High impact information on Acp1

• The transmembrane PTPase CD45 is a key regulator of antigen receptor signalling in T and B cells [6].
• CD45 is a leukocyte-specific, transmembrane protein tyrosine phosphatase (PTPase) required for T cell responsiveness [7].
• Treatment with vanadate did not alter hepatic PTPase activity as assayed in vitro, or receptor and substrate phosphorylation as assayed in vivo, in ob/ob mice despite its substantial effect on blood glucose [8].
• The plasmid-encoded YopH protein is a protein-tyrosine phosphatase (PTPase; EC 3.1.3.48) that is essential for Yersinia virulence [9].
• Our previous results demonstrated that LMW-PTP is able to bind and dephosphorylate activated platelet-derived growth factor receptor (PDGF-r), thus inhibiting cell proliferation [10].

Biological context of Acp1

• On the basis of these results, we propose a key role for LMW-PTP in PDGF-r down-regulation through the dephosphorylation of the activation loop Tyr-857, thus determining a general negative regulation of all downstream signals, with the exception of those elicited by internalized receptors [10].
• The low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme that is involved in the early events of platelet-derived growth factor (PDGF) receptor signal transduction [11].
• It contains both an intrinsic protein tyrosine phosphatase (PTPase) activity and a cytoskeleton binding site in its cytoplasmic domain [12].
• In particular, LMW-PTP is involved in pathways that regulate the transcription of the immediately early genes myc and fos in response to growth factor stimulation [11].
• Constitutive expression of the PTPase by 3T3-L1 preadipocytes using a PTPase HA2 expression vector prevents adipocyte gene expression and differentiation into adipocytes [13].

Anatomical context of Acp1

• Low molecular weight phosphotyrosine phosphatase (LMW-PTP) is an enzyme involved in platelet-derived growth factor-induced mitogenesis and cytoskeleton rearrangement [10].
• NIH 3T3 cells were stably transfected with active or dominant negative LMW-PTP [14].
• Vanadate, a potent PTPase inhibitor, blocks adipocyte differentiation at an early stage in the program, but has no effect on the mitotic clonal expansion required for differentiation [15].
• To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127 [16].
• A tyrosine phosphatase, i.e. PTPase HA2, was previously isolated from 3T3-L1 cells and characterized using O-phospho Tyrosine19-422/aP2 protein (a target of the insulin receptor tyrosine kinase) as substrate [13].

Associations of Acp1 with chemical compounds

• Although AgR-induced protein tyrosine phosphorylation was inhibited by the PTK inhibitors genistein and herbimycin A, it was enhanced by exposure to the PTPase inhibitor phenylarsine oxide (PAO) [17].
• Although the cysteine crucial for PTPase activity resides in domain I, this domain was not active alone [18].
• Moreover, it forms a stable complex with the PTPase: in vitro inhibition of SHP-1 by the drug was not removed by a washing process effective in relieving the inhibition of SHP-1 by the reversible inhibitor suramin [19].
• Consistent with this, our recent studies have demonstrated the existence of a protein tyrosine phosphatase (PTPase), sensitive to the dipeptide aldehyde calpeptin, acting upstream of RhoA [5] [20].
• To address this issue, we have transfected in NIH-3T3 cells a mutant form of LMW-PTP in which the c-Src phosphorylation sites (Tyr(131) and Tyr(132)) were mutated to alanine [11].

Regulatory relationships of Acp1

• The maximum mitogenic response to PDGF and IGF-1 in cells expressing the PTPase was decreased by 67 and 71%, respectively [16].
• Both the effect of somatostatin to stimulate PTPase activity and to inactivate Raf-1 were abrogated by PTx [21].
• PTPase activity stimulated by somatostatin plus GMPPNP was recovered in a peak of high apparent M(r) (670,000) after solubilisation with Triton X-100 and Superose 6 chromatography [21].
• Thus, S49 membranes contain a G-protein regulated PTPase (PTPase-G), and PTPase-G in these cells may reside in a high molecular weight complex [21].
• Interestingly, three out of the four PTPase transcripts induced were the same PTPase transcripts induced during in vitro erythroid differentiation of mouse erythroleukemia (MEL) cells [(1994) J. Biol. Chem. 269, 4709-4712] [corrected] [5].

Other interactions of Acp1

• These DN T cells express a high-molecular-weight isoform of the membrane PTPase CD45 (B220) [22].
• LAR, a transmembrane PTPase expressed in insulin-sensitive tissues, acts as a negative regulator of insulin signaling in intact cell models [23].
• The capacity to produce this second-messenger can be restored by pretreating C3H-gld/gld cells with the PTPase inhibitor, phenylarsine oxide (PAO) [24].
• PTPepsilon was the only PTPase whose transcripts were induced during PC12D cell differentiation among over two dozen PTPase transcripts so far examined [25].
• The Src and signal transducers and activators of transcription pathways as specific targets for low molecular weight phosphotyrosine-protein phosphatase in platelet-derived growth factor signaling [14].

Analytical, diagnostic and therapeutic context of Acp1

• Oligonucleotide-directed mutagenesis was then used to investigate the structural requirements for PTPase activity [18].
• The recombinant protein was isolated by immunoprecipitation with a specific rabbit antiserum and was shown to have protein tyrosine phosphatase (PTPase) activity [18].
• Sequence analysis revealed a transmembrane PTPase containing a single catalytic phosphatase domain that has 45% homology to a rat cytoplasmic brain-specific PTPase named STEP [26].
• By PCR amplification of mouse brain cDNA fragments encoding the catalytic domains of these enzymes, we identified three novel members of the PTPase gene family [26].
• This PTPase cDNA panel, spanning probes for receptor-type as well as cytoplasmic-type family members, was used to monitor RNA expression levels in keratinocyte fractions isolated from murine epidermis and in keratinocyte cell cultures [27].

References