Disease relevance of ANTXR2

• These studies distinguish CMG2 as a second anthrax toxin receptor and identify a potent antitoxin that may prove useful for the treatment of anthrax [1].
• Anthrax toxin receptor 2 mediates Bacillus anthracis killing of macrophages following spore challenge [2].
• Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis [3].
• By contrast, the substitution N657Q significantly reduced toxicity to TEM8 but not CMG2-overexpressing CHO cells [4].
• To extend prior work on targeting of tumor with modified anthrax toxins, we used phage display to select PA variants that preferentially bind to TEM8 as compared with CMG2 [4].

Psychiatry related information on ANTXR2

• To investigate this difference in permissiveness, HCMV infection of both cell types was studied using in situ hybridisation (ISH) as well as immunocytochemistry to detect viral DNA and viral proteins [5].
• The hysteric personality was found significantly more hypnotizable than the other personality types in the HGSHS induction context, whereas the compulsive personality was found significantly more hypnotizable in the ISH induction context [6].
• The Multivariate Personality Inventory (MPI; Magaro & Smith, 1981), the Harvard Group Scale of Hypnotic Susceptibility (HGSHS; Shor & Orne, 1962), and the Inventory of Self-Hypnosis (ISH; Shor, 1970) were used to investigate the relationship between personality style and hypnotic procedure in the determination of hypnotic susceptibility [6].

High impact information on ANTXR2

• LRP6 acts as a coreceptor with either TEM8 or CMG2, the two previously identified receptors for anthrax toxin [7].
• We found that spliced and unspliced viral RNAs could be detected by in situ hybridization (ISH) with specific antisense oligonucleotide probes in lymphocytes and macrophages with sensitivities of fewer than ten copies of spliced viral RNA per cell [8].
• Using the previously reported chromosome 4q21 JHF disease locus as a guide for candidate-gene identification, we identified and characterized JHF and ISH disease-causing mutations in the capillary morphogenesis factor-2 gene (CMG2) [3].
• Although CMG2 encodes a protein upregulated in endothelial cells during capillary formation and was recently shown to function as an anthrax-toxin receptor, its physiologic role is unclear [3].
• Finally, and possibly providing insight into the pathophysiology of these diseases, analysis of fibroblasts derived from patients with JHF or ISH suggests that CMG2 mutations abrogate normal cell interactions with the extracellular matrix [3].

Chemical compound and disease context of ANTXR2

• Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin [9].
• Selection of Anthrax Toxin Protective Antigen Variants That Discriminate between the Cellular Receptors TEM8 and CMG2 and Achieve Targeting of Tumor Cells [4].
• To examine the association of human papillomavirus (HPV) infection with anal squamous cell carcinoma, the authors applied the highly sensitive polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques to detect HPV DNA in formalin-fixed, paraffin-embedded tissues from 18 patients [10].
• To further confirm their EBV association, in situ EBV hybridization (ISH) was performed on tissue biopsies from 15 pediatric HS patients (median age, 3 years and 4 months) using digoxigenin-labeled RNA probes EBER1 [11].
• Additionally, 17 cases of Hodgkin's disease fixed in B5 and formalin were compared for Epstein-Barr encoded RNA detection using RNA ISH with fluorescein isothiocyanate-labeled oligonucleotides [12].

Biological context of ANTXR2

• Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold [13].
• There were no significant differences in levels of fibrin D-dimer or the platelet activation marker soluble P-selectin in the hypertensive patients (i.e. ISH and SDH) compared with control individuals [14].
• We have developed a technique, methylation-specific PCR in situ hybridization (MSP-ISH), which allows for the methylation status of specific DNA sequences to be visualized in individual cells [15].
• Further proof for T-lymphocyte origin of the trisomy 7 and trisomy 10 cells was obtained by simultaneous staining of lymphocytes isolated from tumor tissue with anti-CD3, anti-CD4, and anti-CD8 monoclonal antibodies and ISH [16].
• To identify the type of cells displaying these aneuploidies, we performed in situ hybridization (ISH) with probes specific for the centromeric region of chromosomes 7 and 10 on frozen kidney tissue sections [16].

Anatomical context of ANTXR2

• The protective antigen (PA) protein binds to receptors, either tumor endothelial cell marker 8 (TEM8) or CMG2 (capillary morphogenesis protein 2), and orchestrates the delivery of the lethal and edema factors into the cytosol [4].
• A recombinant portion of CMG-2 was found to bind collagen type IV and laminin, suggesting a potential role in basement membrane matrix synthesis and assembly [17].
• A second novel gene, CMG-2, was found to encode a predicted intracellular protein of 45 kDa containing a transmembrane segment and a CMG-2-GFP chimera was observed to target to the endoplasmic reticulum [17].
• Our results indicate that CMG2 transcripts are preferentially expressed over TEM8 transcripts in primary human and mouse macrophages as compared to immortalized cell lines [18].
• We use MSP-ISH to monitor the timing and consequences of aberrant hypermethylation of the p16 tumor suppresser gene during the progression of cancers of the lung and cervix [15].

Associations of ANTXR2 with chemical compounds

• Here we have tested the requirement for the MIDAS threonine of ANTXR2 for PA-binding [19].
• Labeling of histone H3 mRNA using in situ hybridization (ISH) was assessed as a measure of S-phase cells and compared with that found using in vivo 5-bromodeoxyuridine (BrdUrd) labeling in formalin-fixed rat colonic crypts under baseline, modified 72-h starvation, and 24-h refeeding conditions [20].
• PATIENTS AND METHODS: We retrospectively analyzed RAR-beta mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available [21].
• Using kainic acid (KA) induced epilepsy in rats, the postictal hippocampal expression of synaptopodin was analyzed by in situ hybridization (ISH) and immunohistochemistry [22].
• Neutral buffered formalin (NBF) (4% neutral buffered formaldehyde) has been advocated by most investigators as the primary fixative of choice for in situ hybridization (ISH), and specific anecdotal cautions interdicting the use of precipitating fixatives, which otherwise may offer certain advantages such as superior nuclear detail, are common [12].

Other interactions of ANTXR2

• ISH was performed using a uPA cDNA [23].
• We also showed that binding unmodified ANTXR2 von Willebrand factor A to the prepore in solution enhanced its pore forming activity by slowing its inactivation at acidic pH [24].

Analytical, diagnostic and therapeutic context of ANTXR2

• Northern blot analysis revealed that CMG2 is widely expressed in human tissues, indicating that this receptor is likely to be relevant for disease pathogenesis [1].
• Two ISH family-specific truncating mutations, E220X and the 1-bp insertion P357insC that results in translation of an out-of-frame stop codon, were generated by site-directed mutagenesis and were shown to delete the CMG-2 transmembrane and/or cytosolic domains, respectively [3].
• In this communication, we examined the expression of mRNA transcripts of TEM8 and CMG2 in primary human and mouse macrophages and mouse tissues by standard and quantitative real-time RT-PCR [18].
• METHODS: We examined the expression of this subunit in control and MMIHS tissue derived from patients using in situ hybridization (ISH) and immunocytochemistry (ICC) [25].
• By contrast, most MMIHS tissue gave negative staining with ISH and variable results with ICC [25].

References