Disease relevance of Defcr25

• Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function [1].
• We then created a "library" of phage expressing beta-galactosidase-E1A fusion proteins with a variety of different mutations within CR2 [2].
• We have chosen the adenovirus E1A-retinoblastoma gene product (pRB) proteins for a model system, and we focused on the high-affinity conserved region 2 of adenovirus E1A (CR2) [2].
• The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer [3].
• These findings demonstrate that abnormalities in CR1 and CR2 may be linked to the production of autoantibodies by modifying the effect of other systemic lupus erythematosus susceptibility genes [4].

High impact information on Defcr25

• The (CR2)2-IgG1 chimera competed with cellular CR2 for C3 binding and suppressed the antibody response to a T cell-dependent antigen when administered to mice at the time of immunization [5].
• The ligand for the subunit of the immune system, CD19, is not known, but the complement receptor subunit, CR2 (CD21), binds activation fragments of the C3 component of the complement system and may mediate immunopotentiating effects of complement [5].
• In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG [6].
• We used site-specific mutagenesis to generate a mutant E1A gene with a lysine instead of an aspartic acid at position 121 within the CR2 site [2].
• A lower level of activation was observed for a mutant with a tetrapeptide insertion mapping to conserved region 2 (CR2), a serine- and threonine-rich domain located 100 residues amino-terminal of the kinase domain [7].

Chemical compound and disease context of Defcr25

• Mice (BALB/c) were vaccinated with the HIV-1 gp120 envelope glycoprotein (Env(gp120)) alone or fused to multiple copies of the murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2 binding domain [8].

Biological context of Defcr25

• The in vitro study showed that the CR2 domain is required for E1A-mediated apoptosis, whereas the NH(2)-terminal domain is dispensable [9].
• Wild-type mice were also treated with CR2-Crry, a novel inhibitor of complement activation that targets to sites of C3 deposition [10].
• Recent studies suggest that the Cr2 gene, which encodes for complement receptor (CR)1 and CR2, is important in disease susceptibility [4].
• As immunosuppression is undesirable in patients following SCI, targeted CR2-Crry may provide appropriate bioavailability to treat SCI at a dose that does not significantly affect systemic levels of serum complement activity [10].
• Mutations in the CR1 and CR2 domains have opposing effects on ligand binding affinity, receptor dimerization, tyrosine kinase activation, and signaling competence [11].

Anatomical context of Defcr25

• Despite normal expression of complement receptor 1 (CR1[CD35]) and CR2 (CD21) on follicular dendritic cells, these mice have a profound defect in their capacity to mount a T-dependent antibody response [12].
• CR2-Crry specifically targeted to the injured spinal cord in a distribution pattern corresponding to that seen for deposited C3 [10].
• These findings suggest that CR1/CR2-specific Ab can inhibit the primary Ab response without affecting T helper cells and that the induction of B cell memory is decreased markedly by this treatment [13].
• To compare the roles of CR1 and CR2 on B cells vs FDC in this abnormal response, bone marrow (BM) chimeric mice were generated and immunized with specific T-dependent Ags [14].
• This mutant is unable to transform the Rb-negative fibroblasts, indicating that inactivation of pRb is not the sole function of the CR2-like domain in the induction of transformation of mouse fibroblasts by simian virus 40 [15].

Associations of Defcr25 with chemical compounds

• These data indicate that C5, but not C3d acting through CR2, may play a critical role in the febrile response of mice to i.p. LPS [16].
• In this study, we examined the role of CR2 binding and endogenous complement activation in the antibody response to conjugates of C3d and serotype 14 pneumococcal capsular polysaccharide (PPS14) [17].
• In this study, we chose the factors which are constituents of either a classical or an alternative pathway of a complement system and found that mRNAs corresponding to those of C2, C3, C4, C5 and to those of receptors CR1 and CR2 were expressed [18].
• Similar two-hybrid assays with several truncated forms of Raf-1 showed that both the conserved serine/threonine-rich domain (CR2) and the C-terminal protein kinase domain (CR3) were required for the full inhibition by radicicol [19].

Analytical, diagnostic and therapeutic context of Defcr25

• Quantifying the Activity of Adenoviral E1A CR2 Deletion Mutants Using Renilla Luciferase Bioluminescence and 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography Imaging [3].
• A single intravenous injection of CR2-Crry 1 hour after traumatic injury improved functional outcome and pathology to an extent similar to that seen in C3-deficient animals [10].
• Although the primary SRBC- or KLH-specific IgG response was inhibited markedly (74-98%) by CR1/CR2-specific Ab, no decrease in the number of NIP-specific IgG-producing B cells was detected after secondary immunization [13].
• Recent studies with immunoelectron microscopy indicated that the CR2 was expressed during a systemic infection in a murine model of candidiasis [20].
• The complement C3d-binding protein (CR2) of Candida albicans has been purified by immunoaffinity chromatography, and its specificity has been characterized by immunoblotting with monoclonal antibodies to the C. albicans CR2 and the mammalian CR2 [20].

References