Abstract
Interleukin-15/T(IL-15) is a growth factor that utilizes IL-2 receptor (IL-2R) components in addition to its private binding protein IL-15R(alpha) in T-cells. Here, we report that IL-15 induces mast cell proliferation in the absence of IL-2R alpha and beta. Using transfectants of these cells with a cytoplasmic-truncated mutant of gamma(c), we demonstrated that IL-15 signaling in mast cells does not involve gamma(c). Cross-linking of mast cells with [(125)I]IL-15 revealed a 60-65 kDa IL-15 binding protein that is distinct from known components of T-cell IL-15 receptors. Mast cell IL-15 receptors recruit JAK-2 and STAT-5, instead of JAK1/3 and STAT3/5 that are activated in T-cells. Thus IL-15 is a mast cell growth factor that utilizes a novel receptor and distinct signaling pathway.
MeSH terms
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Animals
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Bone Marrow Cells
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Cell Division / drug effects
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Cell Line
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DNA-Binding Proteins / metabolism
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Humans
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Interleukin-15 / isolation & purification
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Interleukin-15 / metabolism*
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Janus Kinase 1
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Janus Kinase 2
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Mast Cells / metabolism*
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Mice
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Milk Proteins*
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Phosphorylation
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Protein Conformation
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism
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Proto-Oncogene Proteins*
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Receptors, Interleukin-2 / chemistry
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Recombinant Proteins / isolation & purification
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Signal Transduction*
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Structure-Activity Relationship
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TYK2 Kinase
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Trans-Activators / metabolism
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Transfection
Substances
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DNA-Binding Proteins
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Interleukin-15
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Milk Proteins
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Proteins
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Proto-Oncogene Proteins
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Receptors, Interleukin-2
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Recombinant Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Protein-Tyrosine Kinases
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JAK1 protein, human
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JAK2 protein, human
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Jak1 protein, mouse
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Jak2 protein, mouse
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Janus Kinase 1
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Janus Kinase 2
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TYK2 Kinase
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TYK2 protein, human
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Tyk2 protein, mouse