Abstract
G-protein-coupled receptors (GPCRs) typically activate c-Jun N-terminal kinase (JNK) through the G protein betagamma subunit (Gbetagamma), in a manner dependent on Rho family small GTPases, in mammalian cells. Here we show that JNK activation by the prototypic Gq-coupled alpha1B-adrenergic receptor is mediated by the alpha subunit of Gq (Galphaq), not by Gbetagamma, using a transient transfection system in human embryonic kidney cells. JNK activation by the alpha1B-adrenergic receptor/Galphaq was selectively mediated by mitogen-activated protein kinase kinase 4 (MKK4), but not MKK7. Also, MKK4 activation by the alpha1B-adrenergic receptor/Galphaq required c-Src and Rho family small GTPases. Furthermore, activation of the alpha1B-adrenergic receptor stimulated JNK activity through Src family tyrosine kinases and Rho family small GTPases in hamster smooth muscle cells that natively express the alpha1B-adrenergic receptor. Together, these results suggest that the alpha1B-adrenergic receptor/Galphaq may up-regulate JNK activity through a MKK4 pathway dependent on c-Src and Rho family small GTPases in mammalian cells.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cricetinae
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GTP-Binding Protein alpha Subunits, Gq-G11
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GTP-Binding Protein beta Subunits*
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GTP-Binding Protein gamma Subunits*
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Heterotrimeric GTP-Binding Proteins / genetics
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Heterotrimeric GTP-Binding Proteins / physiology*
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Humans
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4*
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MAP Kinase Kinase 7
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MAP Kinase Signaling System*
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Proto-Oncogene Proteins pp60(c-src) / physiology
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Receptors, Adrenergic, alpha-1 / genetics
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Receptors, Adrenergic, alpha-1 / metabolism
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Transfection
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rho GTP-Binding Proteins / physiology
Substances
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ADRA1B protein, human
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G-protein Beta gamma
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Receptors, Adrenergic, alpha-1
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Proto-Oncogene Proteins pp60(c-src)
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP Kinase Kinase 7
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MAP2K4 protein, human
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MAP2K7 protein, human
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Mitogen-Activated Protein Kinase Kinases
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GTP-Binding Protein alpha Subunits, Gq-G11
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Heterotrimeric GTP-Binding Proteins
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rho GTP-Binding Proteins