Disease relevance of Mrs2l

• 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 [1].
• The tyrosine phosphatase RPTP gamma is a candidate tumor suppressor gene since it is located on human chromosome 3p14.2-p21 in a region frequently deleted in certain types of renal and lung carcinomas [2].

High impact information on Mrs2l

• Here we show that dimerization inhibits the activity of a full-length RPTP in vivo [3].
• Here we describe the crystal structure of the membrane-proximal catalytic domain (D1) of a typical RPTP, murine RPTP alpha [4].
• Our results not only demonstrate the biological significance of alternative splicing in the immune system, but also suggest a model for regulating RPTP dimerization and function [5].
• Here we report that RPTP alpha is constitutively phosphorylated on tyrosine in NIH 3T3 mouse fibroblasts [6].
• The in vivo tyrosine phosphorylation site was localized to the C-terminus of RPTP alpha by phosphopeptide mapping experiments using in vivo and in vitro 32P-labeled RPTP alpha [6].

Biological context of Mrs2l

• By contrast, retinoic acid treatment leads to neuronal differentiation of P19 cells, ectopically expressing functional RPTP alpha, as illustrated by their ability to generate action potentials [1].
• The murine RPTP gamma gene has been localized to chromosome 14 to a region syntenic to the location of the human gene [2].
• Characterization of isolated cDNA clones for RPTP showed that the cytoplasmic region contains two tandem repeats of PTP domain of about 230 amino acids with intrinsic phosphatase activity [7].
• To further elucidate the fine tuning of cell growth and differentiation through tyrosine phosphorylation, we tried to isolate mouse receptor-type PTP (RPTP) cDNA clones by screening mouse brain cDNA libraries with mouse CD45 PTP domain probes under reduced-stringency conditions [7].
• PKC down-regulation following prolonged exposure to TPA diminished TPA-stimulated RPTP alpha phosphorylation [8].

Anatomical context of Mrs2l

• The receptor-like protein-tyrosine phosphatase, RPTP alpha, is phosphorylated by protein kinase C on two serines close to the inner face of the plasma membrane [8].
• Previous immunohistochemical studies indicated that both RPTP beta and the extracellular matrix protein tenascin are localized in similar regions of the central nervous system [9].
• The expression pattern of RPTP alpha suggests that RPTP alpha may play a role in neural crest cell differentiation in vivo [10].
• RPTP-kappa expression in both GFP-labeled dorsal root ganglia and SG neurons raises the possibility that homophilic interactions of RPTP-kappa contribute to establishment of connections between specific classes of primary afferent and SG neurons [11].
• SDS-PAGE analysis of three other lymphocyte O-glycoproteins, CD44, CD45, and RPTP alpha, revealed that C2GnT expression resulted in a molecular weight increase of approximately 3-5 kDa for each of these three cell surface glycoproteins [12].

Associations of Mrs2l with chemical compounds

• Previous observations of oxidation of receptor-like PTP (RPTP) alpha after treatment of cells with H(2)O(2) were confirmed [13].
• Immunoprecipitation experiments of cells transfected with RPTP beta expression vector and metabolically labeled with [35S]sulfate and [35S]methionine indicate that the transmembrane form of RPTP beta is indeed a chondroitin sulfate proteoglycan [9].
• P19-EC cells expressing constitutively active RPTP alpha (P19-RPTP alpha) show extensive neuronal differentiation upon RA treatment in monolayer [14].
• Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA) [15].
• We showed that C6 glia-expressed PTPz/RPTP beta stimulated neurite outgrowth by cortical and cerebellar neurons whereas preclustered F3IgFc specifically modified the distribution and intensity of phosphotyrosine labeling in these glial cells [16].

Analytical, diagnostic and therapeutic context of Mrs2l

• RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages [17].
• In situ hybridization analysis reveals that RPTP gamma mRNA is expressed in specific regions of the brain and that the localization of RPTP gamma changes during brain development [2].
• Examination of 293 cells expressing exogenous RPTP alpha using immunofluorescence confocal microscopy showed that RPTP alpha exists predominantly in two subcellular compartments: in dense intracellular granules or dispersed within the plasma membrane [8].
• Sequential polymerase chain reactions established the insertion of the transgene to be in the receptor protein tyrosine phosphatase kappa (RPTP-kappa) and the laminin receptor 1 (ribosomal protein SA) pseudogene 1 locus [11].
• The pharmacological test HPT showed that (-)-(2S,3R)-3.HCl.H2O enantiomer is able to induce opioid-like analgesia with a relative potency 1.5 times that of (2R,3S/2S,3R)-3 and approximately 1.5 times that of morphine [18].

References