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Nerve growth factor signaling involves interaction between the Trk A receptor and lysophosphatidate receptor 1 systems: nuclear translocation of the lysophosphatidate receptor 1 and Trk A receptors in pheochromocytoma 12 cells

We report here that the nerve growth factor (NGF) and lysophosphatidate (LPA) receptor signaling systems interact to regulate the p42/p44 MAPK pathway in PC12 cells. This is based upon several lines of evidence. First, the treatment of PC12 cells, which express LPA 1 receptors, with a sub-maximal co...

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Published in:Cellular signalling 2004, Vol.16 (1), p.127-136
Main Authors: Moughal, Noreen Akhtar, Waters, Catherine, Sambi, Balwinder, Pyne, Susan, Pyne, Nigel J.
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creator Moughal, Noreen Akhtar
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Pyne, Nigel J.
description We report here that the nerve growth factor (NGF) and lysophosphatidate (LPA) receptor signaling systems interact to regulate the p42/p44 MAPK pathway in PC12 cells. This is based upon several lines of evidence. First, the treatment of PC12 cells, which express LPA 1 receptors, with a sub-maximal concentration of LPA and NGF induced synergistic activation of p42/p44 MAPK. Second, the transfection of PC12 cells with LPA 1 receptor anti-sense construct, which reduced the expression of LPA 1, abrogated both LPA- and NGF-stimulated activation of p42/p44 MAPK. Third, the over-expression of recombinant LPA 1 receptor potentiated LPA- and NGF-dependent activation of p42/p44 MAPK. Fourth, the over-expression of C-terminal GRK2 peptide (which sequesters G-protein βγ subunits) or β-arrestin I clathrin binding domain (amino acids: 319–418) or pre-treatment of cells with pertussis toxin reduced the LPA- and NGF-dependent stimulation of p42/p44 MAPK. These findings support a model in which the Trk A receptor uses a G-protein-mediated mechanism to regulate the p42/p44 MAPK pathway. Such G-protein-mediated signaling is activated by the LPA 1 receptor as a means of cross-talk regulation with the Trk A receptor. Fifth, the treatment of cells with LPA induced the transactivation of the Trk A receptor. Sixth, LPA and/or NGF stimulated the translocation of tyrosine phosphorylated Trk A receptor and LPA 1 receptor to the nucleus. Taken together, these findings suggest that NGF and LPA exert cross-talk regulation both at the level of p42/p44 MAPK signaling and in the nuclear translocation of LPA 1 and Trk A receptors.
doi_str_mv 10.1016/j.cellsig.2003.08.004
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Such G-protein-mediated signaling is activated by the LPA 1 receptor as a means of cross-talk regulation with the Trk A receptor. Fifth, the treatment of cells with LPA induced the transactivation of the Trk A receptor. Sixth, LPA and/or NGF stimulated the translocation of tyrosine phosphorylated Trk A receptor and LPA 1 receptor to the nucleus. 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This is based upon several lines of evidence. First, the treatment of PC12 cells, which express LPA 1 receptors, with a sub-maximal concentration of LPA and NGF induced synergistic activation of p42/p44 MAPK. Second, the transfection of PC12 cells with LPA 1 receptor anti-sense construct, which reduced the expression of LPA 1, abrogated both LPA- and NGF-stimulated activation of p42/p44 MAPK. Third, the over-expression of recombinant LPA 1 receptor potentiated LPA- and NGF-dependent activation of p42/p44 MAPK. Fourth, the over-expression of C-terminal GRK2 peptide (which sequesters G-protein βγ subunits) or β-arrestin I clathrin binding domain (amino acids: 319–418) or pre-treatment of cells with pertussis toxin reduced the LPA- and NGF-dependent stimulation of p42/p44 MAPK. These findings support a model in which the Trk A receptor uses a G-protein-mediated mechanism to regulate the p42/p44 MAPK pathway. 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subjects Active Transport, Cell Nucleus - drug effects
Active Transport, Cell Nucleus - genetics
Animals
Cell Nucleus - drug effects
Cell Nucleus - genetics
Cell Nucleus - metabolism
Drug Synergism
Lysophosphatidate
Lysophospholipids - metabolism
Lysophospholipids - pharmacology
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - genetics
Mitogen-Activated Protein Kinase 1 - genetics
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Nerve growth factor
Nerve Growth Factor - metabolism
Nerve Growth Factor - pharmacology
PC12 Cells
Peptide Fragments - pharmacology
Rats
Receptor, trkA - genetics
Receptor, trkA - metabolism
Receptors, G-Protein-Coupled - agonists
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Receptors, Lysophosphatidic Acid
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Transfection
Trk A receptor
title Nerve growth factor signaling involves interaction between the Trk A receptor and lysophosphatidate receptor 1 systems: nuclear translocation of the lysophosphatidate receptor 1 and Trk A receptors in pheochromocytoma 12 cells
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