Abstract
Lnk, SH2-B, and APS form a conserved adaptor protein family. All of those proteins are expressed in mast cells and their possible functions in signaling through c-Kit or FcRI have been speculated. To investigate roles of Lnk, SH2-B or APS in mast cells, we established IL-3-dependent mast cells from Ink-/-, SH2-B-/-, and APS -/- mice. IL-3-dependent growth of those cells was comparable. Proliferation or adhesion mediated by c-Kit as well as degranulation induced by cross-linking FcRI were normal in the absence of Lnk or SH2-B. In contrast, APS-deficient mast cells showed augmented degranulation after cross-linking FcRI compared to wild-type cells, while c-Kit-mediated proliferation and adhesion were kept unaffected. APS-deficient mast cells showed reduced actin assembly at steady state, although their various intracellular responses induced by cross-linking FcRI were indistinguishable compared to wild-type cells. Our results suggest potential roles of APS in controlling actin cytoskeleton and magnitude of degranulation in mast cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / chemistry
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing*
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Calcium / metabolism
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Cell Adhesion
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Cell Division
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Cell Movement
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Cell Separation
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Cell Survival
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Cross-Linking Reagents / pharmacology
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Cytokines / metabolism
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Cytoskeleton / metabolism
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Dose-Response Relationship, Drug
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Electrophoresis, Polyacrylamide Gel
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Flow Cytometry
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Immunoblotting
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Immunohistochemistry
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Interleukin-3 / metabolism
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Intracellular Signaling Peptides and Proteins
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Mast Cells / cytology*
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Mast Cells / metabolism
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Membrane Proteins
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Mice
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Mice, Transgenic
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Protein Binding
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Protein-Tyrosine Kinases / metabolism
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Proteins / chemistry
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Proteins / metabolism
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Proteins / physiology*
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Proto-Oncogene Proteins c-kit / metabolism
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Receptors, Cytokine / metabolism
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Receptors, IgE / chemistry
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Signal Transduction
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Thiazoles / pharmacology
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Thiazolidines
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Time Factors
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Bridged Bicyclo Compounds, Heterocyclic
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Carrier Proteins
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Cross-Linking Reagents
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Cytokines
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Interleukin-3
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Intracellular Signaling Peptides and Proteins
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Lnk protein, mouse
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Membrane Proteins
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Proteins
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Receptors, Cytokine
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Receptors, IgE
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SH2B1 protein, human
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SH2B1 protein, rat
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SH2B3 protein, human
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Sh2b2 protein, mouse
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Sh2b2 protein, rat
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Sh2bpsm1 protein, mouse
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Thiazoles
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Thiazolidines
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-kit
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latrunculin A
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Calcium