Abstract
Angiotensin II stimulates a biphasic activation of Raf-1, MEK, and ERK in WB liver epithelial cells. The first peak of activity is rapid and transient and is followed by a sustained phase. Angiotensin II also causes a rapid activation of p21ras in these cells. Moreover, two Src family kinases (Fyn and Yes) were activated by angiotensin II in a time- and concentration-dependent manner. Microinjection of antibodies against Fyn and Yes blocked angiotensin II-induced DNA synthesis and c-Fos expression in WB cells, indicating an obligatory involvement of these tyrosine kinases in the activation of the ERK cascade by angiotensin II. Finally, substantial reduction of the angiotensin II-stimulated activation of Fyn, Raf-1, ERK, and expression of c-Fos by pertussis toxin pretreatment argues that G proteins of the Gi family as well as the Gq family are involved in angiotensin II-mediated mitogenic pathways in WB cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angiotensin II / pharmacology*
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Animals
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Cell Line
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Enzyme Activation / drug effects
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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GTP-Binding Proteins / metabolism*
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Liver / cytology
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Liver / drug effects*
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Liver / metabolism*
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases*
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-fyn
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Proto-Oncogene Proteins c-raf / metabolism
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Proto-Oncogene Proteins c-yes
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Rats
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Signal Transduction / drug effects
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src-Family Kinases*
Substances
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-fos
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Angiotensin II
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Protein-Tyrosine Kinases
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Fyn protein, rat
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Proto-Oncogene Proteins c-fyn
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Proto-Oncogene Proteins c-yes
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src-Family Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases
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GTP-Binding Proteins