Relaxin signalling in THP-1 cells uses a novel phosphotyrosine-dependent pathway.
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.
Anand-Ivell
Ravinder
R
School of Molecular and Biomedical Sciences, University of Adelaide, SA 5005, Australia.
Heng
Kee
K
Bartsch
Olaf
O
Ivell
Richard
R
D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018000:Receptors, Peptide / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D019000:Phosphotyrosine; D012065:Relaxin; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases