Collagen Mediates Changes in Intracellular Calcium in Primary Mouse Megakaryocytes Through syk-Dependent and -Independent Pathways
We have characterized changes in [Ca2+]iin primary mouse megakaryocytes in response to fibrillar collagen and in response to cross-linking of the collagen receptor, the integrin 2β1. The response to collagen was markedly different from that seen to a triple helical collagen-related peptide (CRP), w...
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Published in | Blood Vol. 93; no. 11; pp. 3847 - 3855 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.1999
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Online Access | Get full text |
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Summary: | We have characterized changes in [Ca2+]iin primary mouse megakaryocytes in response to fibrillar collagen and in response to cross-linking of the collagen receptor, the integrin 2β1. The response to collagen was markedly different from that seen to a triple helical collagen-related peptide (CRP), which signals via the tyrosine kinases p59fyn and p72syk. This peptide binds to the collagen receptor glycoprotein VI (GPVI), but not to the integrin 2β1. Collagen elicited a sustained increase in [Ca2+]i composed primarily of influx of extracellular Ca2+ with some Ca2+release from internal stores. In contrast to CRP, this response was only partially (∼30%) inhibited by the src-family kinase inhibitor PP1 (10 μmol/L) or by microinjection of the tandem SH2 domains of p72syk. Collagen also caused an increase in [Ca2+]i in megakaryocytes deficient in either p59fyn or p72syk, although the response was reduced by approximately 40% in both cases: Cross-linking of the 2 integrin increased [Ca2+]iin these cells exclusively via Ca2+ influx. This response was reduced by approximately 50% after PP1 pretreatment, but was significantly increased in fyn-deficient megakaryocytes. Collagen therefore increases [Ca2+]i in mouse megakaryocytes via multiple receptors, including GPVI, which causes Ca2+ mobilization, and 2β1, which stimulates a substantial influx of extracellular Ca2+. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood.V93.11.3847.411k17_3847_3855 |