Abstract
The heterodimeric peptide hormone relaxin acts through the novel G-protein coupled receptor LGR7 to elicit the production of cAMP in the human monocyte cell line THP-1. The very small number of receptors on the cell surface, and the lack of response in cell membranes imply the involvement of a cytoplasmic signal amplification process. Here we show that this process comprises a novel and specific tyrosine kinase activity close to the receptor, and involves neither protein kinase A, mitogen-activated protein kinase, nor phosphoinositide-3 kinase activities as major upstream components. Furthermore, this novel involvement of a tyrosine kinase activity is cell-type dependent, being largely absent from LGR7-transfected HEK293T cells, and receptor-dependent; vasoactive intestinal peptide or isoproterenol signalling in the same cells does not require this tyrosine kinase activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cyclic AMP / biosynthesis
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / physiology
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Extracellular Signal-Regulated MAP Kinases / physiology
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology
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Organ Specificity
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation
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Phosphotyrosine / metabolism
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Phosphotyrosine / physiology*
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Protein Kinase Inhibitors / pharmacology
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Receptors, G-Protein-Coupled / physiology
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Receptors, Peptide / metabolism
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Relaxin / metabolism*
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Signal Transduction / drug effects
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Transfection
Substances
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Membrane Proteins
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Protein Kinase Inhibitors
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RXFP1 protein, human
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Receptors, G-Protein-Coupled
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Receptors, Peptide
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relaxin receptors
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Phosphotyrosine
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Relaxin
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Cyclic AMP
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Phosphatidylinositol 3-Kinases
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Cyclic AMP-Dependent Protein Kinases
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Extracellular Signal-Regulated MAP Kinases