Differential interactions of thrombospondin-1, -2, and -4 with CD47 and effects on cGMP signaling and ischemic injury responses
| Autor: | William A. Frazier, David D. Roberts, Douglas S. Annis, Malgorzata M. Ptaszynska, Deane F. Mosher, Jeff S. Isenberg, Michael L. Pendrak |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Vascular smooth muscle CD47 Antigen Plasma protein binding Biology Nitric Oxide Biochemistry Nitric oxide chemistry.chemical_compound Mice Ischemia Thrombospondin 1 Animals Humans Receptors Immunologic Cell adhesion Thrombospondins Molecular Biology Cyclic GMP Cells Cultured Mice Knockout CD47 Mechanisms of Signal Transduction Cell Biology Cell biology Mice Inbred C57BL chemistry Immunology Signal transduction Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 284(2) |
| ISSN: | 0021-9258 |
| Popis: | Thrombospondin-1 regulates nitric oxide (NO) signaling in vascular cells via CD47. Because CD47 binding motifs are conserved in the C-terminal signature domains of all five thrombospondins and indirect evidence has implied CD47 interactions with other family members, we compared activities of recombinant signature domains of thrombospondin-1, -2, and -4 to interact with CD47 and modulate cGMP signaling. Signature domains of thrombospondin-2 and -4 were less active than that of thrombospondin-1 for inhibiting binding of radiolabeled signature domain of thrombospondin-1 or SIRPα (signal-regulatory protein) to cells expressing CD47. Consistent with this binding selectivity, the signature domain of thrombospondin-1 was more potent than those of thrombospondin-2 or -4 for inhibiting NO-stimulated cGMP synthesis in vascular smooth muscle cells and downstream effects on cell adhesion. In contrast to thrombospondin-1- and CD47-null cells, primary vascular cells from thrombospondin-2-null mice lack enhanced basal and NO-stimulated cGMP signaling. Effects of endogenous thrombospondin-2 on NO/cGMP signaling could be detected only in thrombospondin-1-null cells. Furthermore, tissue survival of ischemic injury and acute recovery of blood flow in thrombospondin-2-nulls resembles that of wild type mice. Therefore, thrombospondin-1 is the dominant regulator of NO/cGMP signaling via CD47, and its limiting role in acute ischemic injury responses is not shared by thrombospondin-2. |
| Databáze: | OpenAIRE |
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