Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 9, Pages 5000-5008Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0904064
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Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIAAR041101, ZICAR041186] Funding Source: NIH RePORTER
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Engagement of Fc epsilon RI causes its phosphorylation by Lyn kinase. Two alternatively spliced variants, Lyn A and B, are expressed in mast cells, and both isoforms interact with Fc epsilon RI. Unlike Lyn A, Lyn B lacks a 21-aa region in the N-terminal unique domain. In this study, we investigated the role of Lyn A and B isoforms in mast cell signaling and responses. Lyn B was found to be a poor inducer of mast cell degranulation and was less potent in both inositol 1,4,5-triphosphate production and calcium responses. Expression of Lyn B alone showed reduced phosphorylation of both phospholipase C gamma-1 and -2 and decreased interaction of phospholipase C gamma-1 with the phosphorylated linker for activation of T cells. Lyn B also showed increased binding of tyrosine-phosphorylated proteins, which included the negative regulatory lipid phosphatase SHIP-1. In contrast, both Lyn A and B caused similar total cellular tyrosine phosphorylation and Fc epsilon RI phosphorylation and neither Lyn A nor Lyn B alone could completely restore mast cell degranulation or dampen the excessive cytokine production seen in the absence of Lyn. However, expression of both isoforms showed complementation and normalized responses. These findings demonstrate that Lyn B differs from Lyn A in its association with SHIP-1 and in the regulation of calcium responses. However, complementation of both isoforms is required in mast cell activation. The Journal of Immunology, 2010, 184: 5000-5008.
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