Abstract
G-protein-coupled receptors are a large group of integral membranal receptors, which in response to ligand binding initiate diverse downstream signaling. Here we studied the gonadotropin-releasing hormone (GnRH) receptor, which uses Gq for its downstream signaling. We show that extracellular signal-regulated kinase (ERK) activation is fully dependent on protein kinase C (PKC), but only partially dependent on Src, dynamin, and Ras. Receptor tyrosine kinases, FAK, Gbetagamma, and beta-arrestin, which were implicated in some G-protein-coupled receptor signaling to MAPK cascades, do not play a role in the GnRH to ERK pathway. Our results suggest that the activation of ERK by GnRH involves two distinct signaling pathways, which converge at the level of Raf-1. The main pathway involves a direct activation of Raf-1 by PKC, and this step is partially dependent on a second pathway consisting of Ras activation, which occurs in a dynamin-dependent manner, downstream of Src.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Animals
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Arrestins / physiology
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Cell Line
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Dynamins
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ErbB Receptors / physiology
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Focal Adhesion Protein-Tyrosine Kinases
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GTP Phosphohydrolases / physiology*
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Gonadotropin-Releasing Hormone / pharmacology*
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Heterotrimeric GTP-Binding Proteins / physiology
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MAP Kinase Signaling System
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Models, Biological
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Protein Kinase C / metabolism*
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Protein-Tyrosine Kinases / physiology
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Proto-Oncogene Proteins c-raf / metabolism
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Proto-Oncogene Proteins p21(ras) / physiology*
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Proto-Oncogene Proteins pp60(c-src) / physiology*
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beta-Arrestins
Substances
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Arrestins
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beta-Arrestins
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Gonadotropin-Releasing Hormone
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ErbB Receptors
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Protein-Tyrosine Kinases
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Focal Adhesion Protein-Tyrosine Kinases
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Proto-Oncogene Proteins pp60(c-src)
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Proto-Oncogene Proteins c-raf
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Protein Kinase C
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Mitogen-Activated Protein Kinase 1
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GTP Phosphohydrolases
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Heterotrimeric GTP-Binding Proteins
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Proto-Oncogene Proteins p21(ras)
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Dynamins