Disease relevance of PRG2

• Eosinophil granule MBP is initially translated as a nontoxic precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is believed to neutralize MBP toxicity [1].
• In addition, this form of SCF induced the expression of a pertussis toxin-sensitive G(i) protein, G(i3) that interacts with MBP to trigger mast cell non-IgE-dependent activation in a manner similar to other cationic compounds such as compound 48/80 [2].
• EMBP is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases such as asthma [3].
• Eosinophil-derived agents such as PAF, LTC4, MBP and ECP might be responsible for submucosal oedema and non-specific bronchial hyperreactivity which are characteristic features of late-phase reactions [4].
• In bronchial asthma, considerable evidence exists that the eosinophil releases granule proteins, especially the major basic protein (MBP), which in turn mediate tissue abnormalities [5].

Psychiatry related information on PRG2

• The presence in CSF of MS patients of a cross-reactive Id to different MBP peptides is indicative of an immune response to this encephalitogenic myelin protein in a segment of MS patients [6].
• The mean counts per minute (cpm) value of serum anti-MBP antibody of the catatonia group was significantly higher than that of the patients with other forms of schizophrenic psychoses (p less than .05) [7].
• An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI) [8].
• Results show that increased CSF levels of MBP were detected in all patients with severe ADC (10/10) and, less often, in subjects with mild (2/7) or moderate dementia (7/16) [9].
• Based on a suspected pathological relationship of autoimmunity in Alzheimer's disease (AD), antibodies to myelin basic protein (MBP) were investigated in the sera of AD patients, healthy controls and disease controls [10].

High impact information on PRG2

• A panel of 129 peptides that matched the molecular mimicry motif was tested on seven MBP-specific T cell clones from multiple sclerosis patients [11].
• Transgenic mice developed experimental allergic encephalomyelitis (EAE) following immunization with MBP and adjuvant plus pertussis toxin as well as with administration of pertussis toxin alone [12].
• T cell responses to the inoculates were induced to deplete circulating MBP-reactive T cells in the recipients [13].
• A major epitope of myelin basic protein (MBP), p87-99 (VHFFKNIVTPRTP), induces experimental autoimmune encephalomyelitis (EAE) [14].
• A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue [15].

Chemical compound and disease context of PRG2

• A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone [16].
• Preincubation with 0.01 to 3 micrograms/mL pertussis toxin did not inhibit MBP-stimulated O2- production, and MBP did not stimulate an increase in diradylglycerol levels [17].
• Specific binding and the presence of saturable binding sites for 3H-labeled estramustine were demonstrated in astrocytoma tissues expressing EMBP-like protein [18].
• A single-step propidium iodide exclusion assay was then used to show that EPO + MBP in the absence of hydrogen peroxide is substantially cytotoxic only to the acute lymphocytic leukemia and IM-9 cells [19].
• Two proton ionophores (DNP and carbonyl cyanide m-chlorophenyl hydrazone) protected E. coli from the bactericidal effects of ECP but not from MBP [20].

Biological context of PRG2

• Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event [21].
• RESULT(S): Major basic protein (MBP) is found in several ovarian cell types throughout the menstrual cycle [22].
• 9. A cDNA for human MBP was isolated from a gamma GT10 HL-60 cDNA library [23].
• The nucleotide sequence of the MBP cDNA indicates that MBP is translated as a 25.2-kD preproprotein [23].
• Genistein and the Src kinase family inhibitor, 4-amino-5-(4-methyphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, inhibited MBP-stimulated phosphorylation of Akt [24].

Anatomical context of PRG2

• Proteinase inhibition by proform of eosinophil major basic protein (pro-MBP) is a multistep process of intra- and intermolecular disulfide rearrangements [25].
• By in situ hybridization, PAPP-A mRNA is detected in placental X cells and syncytiotrophoblasts, but MBP mRNA is localized only to placental X cells [1].
• RESULTS: Immunofluorescence staining with proMBP absorbed anti-PAPP-A antibody showed that PAPP-A is localized to placental septa, anchoring villi, and the syncytia of chorionic villi, whereas MBP is localized only to septa and anchoring villi [1].
• The luteal tissue is the major site of MBP and PAPP-A with highest intensity found during the midluteal phase associated with both small and large luteal cells [22].
• In the intermediate/mature follicles, MBP was immunolocalized in theca, but not in granulosa cells except in the mature follicles [22].

Associations of PRG2 with chemical compounds

• The pro-MBP subunit contains 12 cysteine residues, of which 10 have been accounted for [26].
• Eosinophil granule major basic protein (MBP), a potent toxin for helminths and various cell types, is a 13.8-kD single polypeptide rich in arginine with a calculated isoelectric point (pI) of 10 [23].
• The NH2-terminal half has a predicted pI of 3.7 and is hydrophilic, while the COOH-terminal half (corresponding to mature MBP) has a predicted pI of 11.1 and is hydrophobic [27].
• In fact, cord blood-derived mast cells cocultured with 3T3 in the presence of antisense for SCF or cocultured with fibroblasts that do not express the membrane form of SCF were inhibited in their histamine-releasing activity toward MBP [2].
• Our analysis suggests that EMBP specifically binds heparin [3].

Physical interactions of PRG2

• However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1 [28].

Regulatory relationships of PRG2

• These findings show that SCF significantly influences mast cell differentiation and the responsiveness of mast cells to eosinophil-derived granule MBP [29].
• MBP stimulated 2-fold increases in IL-8 messenger RNA (mRNA) after 1 and 3 h of incubation, which were blocked by pretreatment with actinomycin D [28].
• The MBP-induced upregulation of TNF-alpha and LT was major histocompatibility complex (MHC) class II molecule dependent [30].
• Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF [31].

Other interactions of PRG2

• In addition, it is shown that commercial polyclonal anti-PAPP-A is polyspecific, also reacting with MBP [32].
• We have defined a novel synergistic, as opposed to antagonistic, combinatorial interaction between GATA-1 and PU.1, and a unique repressor role for certain C/EBPepsilon isoforms in the transcriptional regulation of a model eosinophil granulocyte gene, the major basic protein (MBP) [33].
• IL-5-like products from these putative activated lymphocytes might perpetuate (a) eosinophil production by the bone marrow, (b) its release into the circulation, (c) its migration into bronchial tissue and (d) activation to release PAF, LTC4, MBP, etc.(ABSTRACT TRUNCATED AT 400 WORDS)[4]
• The fibroblast-derived membrane form of stem cell factor (SCF) was found to be involved in the mast cell increased responsiveness to MBP [2].
• To determine the functionality of this site, we tested whether GATA-1 and GATA-2, either individually or in combination, can transactivate the MBP promoter in the Jurkat T cell line [34].

Analytical, diagnostic and therapeutic context of PRG2

• The results are the outcome of analysis of tryptic and CNBr/tryptic peptides from PAPP-A/proMBP, sequence analysis of intact and reduced and carboxymethylated PAPP-A/proMBP, and reaction with monoclonal antibodies directed against MBP and its proform [32].
• Concentrations of a molecule immunochemically similar to eosinophil granule MBP are present in maternal plasma, and MBP mRNA has been localized to placental X cells by in situ hybridization [1].
• DESIGN: Ovarian tissues (n = 50) and corpora lutea (n = 18) were obtained from patients undergoing hysterectomy/oophorectomy for benign conditions and tissue sections were immunostained for MBP and PAPP-A [22].
• Here we report that highly purified human lung mast cells became responsive to eosinophil major basic protein (MBP) when in coculture with human lung fibroblasts [2].
• Characterization of MBP by reverse-phase high pressure liquid chromatography and two-dimensional gel analysis showed no microheterogeneity that might be attributed to post-translational modifications [35].

References