Domain-specific interactions between entactin and neutrophil integrins. G2 domain ligation of integrin alpha3beta1 and E domain ligation of the leukocyte response integrin signal for different responses
| Autor: | H D, Gresham, I L, Graham, G L, Griffin, J C, Hsieh, L J, Dong, A E, Chung, R M, Senior |
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| Rok vydání: | 1996 |
| Předmět: |
Integrins
Binding Sites Membrane Glycoproteins Integrin alpha3 Neutrophils Integrin beta1 Macrophage-1 Antigen Metalloendopeptidases CD47 Antigen Antigen-Antibody Complex Receptors Fc Ligands Chemotaxis Leukocyte Phagocytosis Antigens CD Matrix Metalloproteinase 7 Humans Carrier Proteins Oligopeptides |
| Zdroj: | The Journal of biological chemistry. 271(48) |
| ISSN: | 0021-9258 |
| Popis: | Extracellular matrix proteins activate neutrophils to up-regulate many physiologic functions that are necessary at sites of tissue injury. To elucidate the ligand-receptor interactions that mediate these functions, we examined neutrophil activation by the basement membrane protein, entactin. Entactin is structurally and functionally organized into distinct domains; therefore, we utilized glutathione S-transferase -fusion proteins encompassing its four major domains, G1, G2, E, and G3, to assess interactions between entactin and neutrophil integrin receptors. We show that the E domain, which contains the single RGD sequence of entactin, is sufficient for ligation of the beta3-like integrin, leukocyte response integrin, and signaling for chemotaxis. Moreover, the G2 domain signals for stimulation of Fc receptor-mediated phagocytosis via ligation of alpha3beta1. This receptor-ligand interaction was revealed only after stimulation of neutrophil by immune complexes or phorbol esters. Interestingly, the E domain does not enhance phagocytosis, and the G2 domain is not chemotactic. Furthermore, cleavage of entactin with the matrix metalloproteinase, matrilysin, liberates peptides that retain E domain-mediated chemotaxis and G2 domain-mediated enhancement of phagocytosis. These studies indicate that multiple domains of entactin have the ability to ligate individual integrins expressed by neutrophils and to activate distinct functions. |
| Databáze: | OpenAIRE |
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