Table 2.
Functions of CD47 isoforms and domains.
| Functions | Cell type | IgV domain | MMS domain | Cytoplasmic tails | Isoforms |
|---|---|---|---|---|---|
| CD47 interacts with αv integrin to mediate Vn-bead binding (56). | Human ovarian carcinoma cell line OV10 | Sufficient | Dispensable | Dispensable | Four isoforms contribute equally. |
| CD47–αvβ3 complexes in cyclodextrin-resistant domains promote integrin activation induced by RGD peptide and αvβ3 avidity for binding immobilized substrates by enhancing integrin clustering (68). | Sufficient | Dispensable | – | – | |
| CD47–αvβ3 complexes in cyclodextrin-sensitive cholesterol-rich raft are involved in Gi-dependent signaling (68). | Necessary | Necessary | – | – | |
| PLICs bind to cytoplasmic tails of CD47 and induce the redistribution of vimentin and cell spreading (13). | – | – | Tails of iso-2 and iso-4 directly interact with PLICs. | ||
| CD47 costimulates T-cell activation with TCR via an adhesion-dependent and CD28-independent signaling pathway (12). | Human T lymphocyte leukemia cell line Jurkat | Necessary | Necessary | Dispensable | Iso-1 and iso-2 contribute equally. |
| CD47 costimulates T-cell activation and enhances TCR signaling by promoting T-cell spread on APC or surface (57). | Necessary | Necessary | Dispensable | Iso-1 and iso-2 contribute equally. | |
| The long-range disulfide bond between the IgV and MMS domains is required for binding of anti-Ig domain monoclonal antibodies and SIRPα (51). | Necessary | Necessary | – | – | |
| CD47 induces caspase-independent cell death (normal and leukemic cells) by triggering phagocytotic signaling by human DCs (55). | Necessary | Necessary | Dispensable | Iso-1 and iso-2 contribute equally. | |
| BNIP3 colocalizes with CD47 on the membrane but translocates to the mitochondria to induce mitochondrial depolarization and T-cell death after stimulation via CD47/TSP-1 (14). | Ineffective | Necessary | Inconclusive | – | |
| CD47 interacts with and switches αIIbβ3 to a high-affinity state to induce platelet aggregation (67). | Human B-lymphocytic cell line Namalwa; Chinese hamster ovary (CHO) cells | Sufficient | Dispensable | Dispensable | – |
| CD47 promotes neurite formation by activating the members of the Rho family of small G proteins Rac and Cdc42 (10). | Mouse neuroblastoma cell line N1E-115; H-Ra-transformed CHO cell | Sufficient | Dispensable | Dispensable | Iso-1 and iso-2 contribute equally. |
| CD47-dependent formation of filopodia in cells plated on SIRPα–Fc is mediated predominantly through Cdc42 activation (10). | Partially effective | Partially effective | Partially effective | – | |
| Differential localization of SIRPα and CD47 at axons and dendrites regulates synaptogenesis and formation of neural networks (66). | Hippocampal cells | Necessary | Ineffective | Dispensable | – |
| CD47 is thought to be closely associated with memory consolidation in rats (54). | – | – | – | Iso-3 and iso-4 are associated with memory consolidation. | |
| CD47 regulates cell–cell adhesion and cell migration through reorganization of actin cytoskeleton in epithelial cells (65). | Madin–Darby canine kidney cells | Partially participates in lamellipodium formation. | Required for localization of CD47 at cell–cell adhesion sites and lamellipodium formation. | Dispensable | – |
IgV, immunoglobulin variable; Iso, isoform; MMS, multiple membrane-spanning; TCR, T-cell receptor; -, no data.