Disease relevance of CD47

• CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia [1].
• CD47-SIRPalpha may represent a potential pathway for the control of hemolytic anemia [2].
• Absence of CD47 in protein 4.2-deficient hereditary spherocytosis in man: an interaction between the Rh complex and the band 3 complex [3].
• Pertussis toxin (PTX) prevented CD47-mediated death, indicating the involvement of Gi alpha [4].
• TSP1, peptides, and a recombinant fragment from the type I repeats, but not peptides that bind CD36 or CD47, inhibit the proliferation of A2058 melanoma cells [5].
• CD47 is an important biomarker in breast cancer, and functions as a prognostic factor for DFS [6].

Psychiatry related information on CD47

• Few nucleic acids have been characterized in either scrapie or CJD, but previous cloning experiments delineated relatively short LTR regions of the endogenous IAP retrovirus in 120S CJD preparations [7].
• IAP-catalyzed [32P]ADP-ribosylation was not significantly different between patients and controls, suggesting that the quantity of IAP-sensitive G proteins is unaltered in affective disorder patients [8].

High impact information on CD47

• The Rh antigen is a multi-subunit complex composed of Rh polypeptides and associated glycoproteins (Rh50, CD47, LW and glycophorin B); these interact in the red cell membrane and are lacking or severely reduced in Rhnull cells [9].
• Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia [10].
• Furthermore, pretreatment of cells with IAP (islet-activating protein from the bacterium Bordetella pertussis) eliminates the ACh-induced inward rectification [11].
• As IAP specifically ADP-ribosylates two GTP-binding proteins, Ni and No, that can interact with mAChRs, we conclude that a guanyl nucleotide-binding protein couples ACh binding to channel activation [11].
• Opioid inhibition of adenylyl cyclase has been reconstituted in IAP-treated NG108-15 cell membranes with a Gi preparation from brain [12].

Chemical compound and disease context of CD47

• We examined the regulation of alpha4beta1 integrin function in melanoma cells and T cells by ligands of CD47 [13].
• It is unknown whether CD47 has an impact on AIHA of the warm type or autoimmune thrombocytopenia (ITP) in humans [14].
• The monoclonal antibody OVTL3 has a highly restricted reactivity with ovarian carcinomas and defines a surface glycoprotein, OA3, which has been used for immunotargeting [15].
• To determine whether progesterone inhibition is mediated by the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase, Ni, the effect of the Bordetella pertussis toxin (IAP) and limited proteolysis on progesterone action in oocytes was investigated [16] .

Biological context of CD47

• Integrin-associated protein (IAP/CD47) augments the function of alpha2beta1 integrin in smooth muscle cells (SMC), resulting in enhanced chemotaxis toward soluble collagen (Wang, X-Q., and W.A. Frazier. 1998. Mol. Biol. Cell. 9:865) [17].
• In normal cells, Rh phenotype influences CD47 expression but not the level of membrane skeleton attachment of CD47 [18].
• Thrombospondin-1 acts via IAP/CD47 to synergize with collagen in alpha2beta1-mediated platelet activation [19].
• Forskolin, 8-bromo cAMP, and isobutylmethylxanthine (IBMX) all prevented CD47-mediated apoptosis, indicating the involvement of cAMP [4].
• Moreover, SIRPalpha1 in each of the two cell lines recruited SHP-2 on phosphorylation, and SIRPalpha1 phosphorylation in cultured cells is CD47 dependent [20].

Anatomical context of CD47

• Role of CD47 as a marker of self on red blood cells [2].
• Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign [2].
• Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior [21].
• The release of TSP-1 by DCs in response to ATP was confirmed at the protein level by enzyme-linked immunosorbent assay (ELISA), immunodetection, and mass spectrometry analysis, and has an antiproliferative effect on T CD4+ lymphocytes through TSP-1/CD47 interaction [22].
• In addition, CD47-mediated adhesion of human and pig RBCs to SIRPalpha1 surfaces resists sustained forces in centrifugation (as confirmed by atomic force microscopy) but only at SIRPalpha-coating densities far above those measurable on human neutrophils, monocytes, and THP-1 macrophages [23].

Associations of CD47 with chemical compounds

• CD47-activated SS RBC adhesion absolutely requires the Src family tyrosine kinases and is also enhanced by treatment of SS RBCs with low concentrations of cytochalasin D, which may release alpha4beta1 from cytoskeletal restraints [24].
• CD47 signaling in SS RBCs appears to be independent of large scale changes in cAMP formation but nonetheless promotes alpha4beta1-mediated adhesion via a protein kinase A-dependent, serine phosphorylation of the alpha4 cytoplasmic domain [24].
• In addition, several membrane components including the Rh proteins and other glycoproteins recently characterized (Rh50 glycoprotein, CD47, glycophorin B, Duffy, LW) are absent or severely decreased on these cells [25].
• The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells [26].
• Cholesterol-independent interactions with CD47 enhance alphavbeta3 avidity [27].

Physical interactions of CD47

• We investigated the mechanism by which TS-bound IAP modulates the affinity of platelet integrin, alphaIIbbeta3 [28].
• CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis [29].
• CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPalpha) [2].
• Both alphaIIb and beta3 integrin subunits and c-Src bind along with IAP [30].
• Site-directed mutagenesis and gel electrophoretic mobility shift assay identified a alpha-Pal/NRF-1 binding element within the IAP core promoter [31].

Co-localisations of CD47

• CD47 is colocalized with E-cadherin at cell-cell adhesion sites of epithelial cells [32].

Regulatory relationships of CD47

• However, the CD47-activated SS RBC adhesion receptor(s) that mediated adhesion to immobilized TSP remained unknown [24].
• Interaction between CD47 and the BH3-only protein was confirmed by immunoprecipitation analysis, and CD47-induced apoptosis was inhibited by attenuating BNIP3 expression with antisense oligonucleotides [29].
• Human CD47-expressing CHO cells spread rapidly on SIRPalpha-coated glass surfaces, correlating well with the spreading of primary human T cells [33].
• We recently reported that CD47 ligation inhibited IL-2 release by umbilical cord blood mononuclear cells activated in the presence of IL-12, but not IL-4, preventing the induction of IL-12Rbeta(2) expression and the acquisition of Th1, but not the Th2 phenotype [34].
• The failure of IAP to activate Jurkat together with CD16-7-zeta correlated with a lack of c-Jun N-terminal kinase, but not extracellular-signal-regulated kinase activation [35].

Other interactions of CD47

• A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities [21].
• Using CD47 as bait in a yeast two-hybrid system, we identified the Bcl-2 homology 3 (BH3)-only protein 19 kDa interacting protein-3 (BNIP3), a pro-apoptotic member of the Bcl-2 family, as a novel partner [29].
• Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28 [35].
• This group includes the Rh50 glycoprotein, LW glycoprotein, glycophorin B, Duffy glycoprotein, and CD47 glycoprotein [36].
• Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family [37].

Analytical, diagnostic and therapeutic context of CD47

• Here we report that CD47, its beta3 integrin partner, and Gi proteins form a stable, detergent-soluble complex that can be recovered by immunoprecipitation and affinity chromatography [38].
• Immunofluorescence analysis of CD47 and BNIP3 revealed a partial colocalization of both molecules under basal conditions [29].
• A direct interaction between human SIRP and human CD47 was demonstrated using purified recombinant proteins and surface plasmon resonance ruling out the involvement of other proteins known to be associated with CD47 [39].
• In contrast to SIRPalpha1 and SIRPalpha2, no adhesion of SIRPbeta1 to CD47 could be detected by cell attachment assays and flow cytometry [40].
• Flow cytometric and immunoblotting analysis revealed a severe reduction of CD47 (up to 80%) and a slower mobility of RhAG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, possibly reflecting an overglycosylation state [41].

References