Disease relevance of Ptprz1

• Taken together, these data indicate that erroneous Ptprz signaling induces gastric ulcers [1].
• Reverse transcription-polymerase chain reaction analyses indicate that human PTP zeta is highly expressed in a glioblastoma cell line [2].
• We observed a strong binding of F3IgFc-coated fluorospheres to astrocytes in neural primary cultures and to C6 astrocytoma cells, and demonstrated, in antibody perturbation experiments, that F3-Ig binding on astrocytes depends on its interaction with PTPzeta/RPTPbeta [3].
• Neonatal dorsal root ganglion (DRG) explants grown on a rich supportive substrate (laminin) with and without DSD-1-PG were strikingly inhibited by the proteoglycan [4].
• Further characterization of DSD-1-PG has included sequencing of peptides from the core protein and the cloning of the corresponding cDNA using polyclonal antisera against DSD-1-PG to screen phage expression libraries [4].

High impact information on Ptprz1

• Primary cultures of gastric epithelial cells from Ptprz+/+ and Ptprz-/- mice also showed similar incorporation of VacA, cellular vacuolation and reduction in cellular proliferation, but only Ptprz+/+ cells showed marked detachment from a reconstituted basement membrane 24 h after treatment with VacA [1].
• Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons [5].
• Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal [6].
• Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini [6].
• We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin [6].

Chemical compound and disease context of Ptprz1

• A receptor-type protein tyrosine phosphatase PTP zeta is expressed in human cutaneous melanomas [7].

Biological context of Ptprz1

• Together, the spatiotemporal expression patterns of neurocan and phosphacan indicate that these chondroitin sulfate proteoglycans have diverse in situ roles, which are dependent on context-specific interactions with extracellular and cell adhesion molecules within the developing olfactory nerve pathway [8].
• The deduced amino acid sequence of human PTP zeta is composed of a putative signal peptide of 19 amino acids, a very large extracellular domain of 1616 amino acids, a transmembrane peptide of 26 amino acids, and a cytoplasmic domain of 653 amino acids [2].
• The human gene encoding this phosphatase, denoted RPTP beta (or PTP zeta), has been localized to chromosome 7q31-33 [9].
• Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan [10].
• At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed [11].

Anatomical context of Ptprz1

• Phosphacan short isoform, a novel non-proteoglycan variant of phosphacan/receptor protein tyrosine phosphatase-beta, interacts with neuronal receptors and promotes neurite outgrowth [12].
• The expression of the PSI protein varies during central nervous system development in a fashion similar to that observed for phosphacan, being first detected around embryonic day 16 and then showing a dramatic increase in expression to plateau around the second week post-natal [12].
• Phosphacan, unlike neurocan, was present within the mesenchyme surrounding the E11.5 and E12.5 nasal cavity [8].
• Furthermore, the phosphacan-related molecule neutralizes growth cone repulsion induced by TN-R coated as a sharp substrate boundary with or without prior treatment with chondroitinase ABC [10].
• Phosphacan was detected from neuronal culture supernatants of cortical, hippocampal, and cerebellar neurons, but not from type-1 astrocytes using 6B4 and 3F8 antibodies [13].

Associations of Ptprz1 with chemical compounds

• The extracellular portion of human PTP zeta contains two striking structural features: the N-terminal 280-amino acid sequence that is homologous to carbonic anhydrases (carbonate hydro-lyase, EC 4.2.1.1), and a sequence of 1048 amino acids without a cysteine residue [2].
• We affinity-isolated tenascin-C and isoforms of the proteoglycan-type protein tyrosine phosphatases zeta/beta (PTPzeta/RPTPbeta) from extracts of developing mouse brain [3].
• C6 glia-expressed PTPzeta/RPTPbeta stimulated neurite outgrowth by cortical and cerebellar neurons, whereas preclustered F3IgFc specifically modified the distribution of phosphotyrosine labelling in these glial cells [3].
• The inhibitory effects of DSD-1-PG on the DRG explants were not relieved by removal of the CS GAGs, indicating that this activity is associated with the core glycoprotein [4].
• DSD-1-PG is a chondroitin sulfate proteoglycan (CSPG) expressed by glial cells that can promote neurite outgrowth from rat embryonic mesencephalic (E14) and hippocampal (E18) neurons, an activity that is associated with the CS glycosaminoglycans (GAGs) [4].

Physical interactions of Ptprz1

• These observations indicate that TN-R can interact with a phosphacan-related molecule and thereby modulate its inhibitory influence on neuritogenesis [10].
• These results suggested that Arg78 in midkine plays an essential role in high affinity binding to PTPzeta by interacting with the chondroitin sulfate portion of this receptor [14].
• Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase zeta (PTPzeta) with high affinity [14].

Regulatory relationships of Ptprz1

• In developing mice brain high levels of PTP zeta have been detected indicating its developmental importance; PTP zeta is also expressed in glioblastoma and neuroblastoma [7].

Other interactions of Ptprz1

• We report here the identification of a novel truncated form of phosphacan, phosphacan short isoform (PSI), that corresponds to the N-terminal carbonic anhydrase- and fibronectin type III-like domains and half of the spacer region [12].
• This protein is post-translationally modified with oligosaccharides, including the HNK-1 epitope, but, unlike phosphacan, it is not a proteoglycan [12].
• Phosphacan, one of the principal proteoglycans in the extracellular matrix of the central nervous system, is implicated in neuron-glia interactions associated with neuronal differentiation and myelination [12].
• The chondroitin sulfate proteoglycans neurocan and phosphacan are believed to modulate neurite outgrowth by binding to cell adhesion molecules, tenascin, and the differentiation factors heparin-binding growth-associated molecule and amphoterin [8].
• Within the embryonic olfactory bulb, phosphacan was localised to the external and internal plexiform layers [8].

Analytical, diagnostic and therapeutic context of Ptprz1

• Light microscopic immunohistochemistry showed that 6B4 RPTPbeta/phosphacan immunoreactivity was observed around neurons in the cortical plate [13].
• In this study, expression and localization of RPTPbeta and phosphacan were examined in developing neurons by immunological analyses using 6B4, 3F8, and anti-PTP antibodies and reverse transcription-polymerase chain reaction (RT-PCR) [13].
• We generated mice in which the PTPzeta gene was replaced by the LacZ gene by gene targeting [15].
• In order to study the regulation of DSD-1-PG expression, an in vitro enzyme-linked immunosorbent assay based on Oli-neu and mAb 473HD was established [16].
• Biochemical and immunoprecipitation studies performed with biosynthetically labelled Oli-neu and primary neural cells demonstrated that DSD-1-PG is expressed in vitro as a proteoglycan of 1000 kD apparent Mr with two core glycoproteins of 250 kD and 400 kD [16].

References