Abstract
The protein tyrosine kinase Syk is an essential element in several cascades coupling Ag receptors to cell responses. Syk and the mitogen-activated protein kinase extracellular signal-regulated kinase 1 (ERK1) were found to form a tight complex in both resting and Ag-stimulated rat mucosal-type mast cells (rat basophilic leukemia 2H3 cell line RBL-2H3). A direct serine phosphorylation and activation of Syk by ERK was observed in in vitro experiments. Moreover the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase (MEK) inhibitors markedly decreased the Ag-induced phosphorylation of the tyrosyl residues of Syk and its activation as well as suppressed the degranulation of the cells. These results suggest a positive feedback regulation of Syk by ERK in the cascade coupling the type 1 Fc epsilon receptor to the secretory response of mast cells; hence, the existence of a novel type of cross-talk between protein serine/threonine kinases and protein tyrosine kinases is suggested.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / isolation & purification
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cell Degranulation / drug effects
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Cell Degranulation / immunology
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Enzyme Inhibitors / pharmacology
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Enzyme Precursors / antagonists & inhibitors
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Enzyme Precursors / genetics
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Enzyme Precursors / isolation & purification
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Enzyme Precursors / metabolism*
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Feedback
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Intracellular Signaling Peptides and Proteins
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Leukemia, Basophilic, Acute
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MAP Kinase Kinase Kinase 1*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / isolation & purification
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Protein-Tyrosine Kinases / metabolism*
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Rats
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Receptors, IgE / physiology*
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Recombinant Proteins / metabolism
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Signal Transduction / immunology*
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Subcellular Fractions / enzymology
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Syk Kinase
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Tumor Cells, Cultured
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Tyrosine / metabolism
Substances
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Antigens
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Enzyme Inhibitors
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Enzyme Precursors
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Intracellular Signaling Peptides and Proteins
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Receptors, IgE
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Recombinant Proteins
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Tyrosine
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Syk protein, rat
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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MAP3K1 protein, human