Overexpression of c-src enhances beta-adrenergic-induced cAMP accumulation.
Proc Natl Acad Sci U S A
; 87(19): 7462-6, 1990 Oct.
Article
em En
| MEDLINE
| ID: mdl-1699227
ABSTRACT
During our investigations into the physiological role of c-src tyrosine kinase in normal cells, we found that clonal transfectants of C3H10T1/2 murine fibroblasts overexpressing chicken c-src exhibited strikingly elevated levels of cAMP accumulation in response to adrenergic stimulation as compared to control cells. Enhanced cAMP accumulations were detected when cells were treated with the beta-agonists, epinephrine, isoproterenol, or terbutaline and were blocked by treatment with the beta-specific antagonist propranolol, indicating action through beta-adrenergic receptors. The hyperresponsiveness was not observed in cells overexpressing kinase-defective c-src. No differences in basal levels of cAMP, agonist concentration dependence, or kinetics of cAMP accumulation were detected between cells containing elevated levels of wild-type or kinase-defective c-src protein and control cells. To determine if the degree of c-src overexpression could influence the response, multiple clones, transfected with DNA encoding genes for wild-type or kinase-defective c-src plus neomycin resistance or neomycin resistance alone, were derived in parallel and assayed for the amounts of c-src protein produced and the levels of cAMP accumulated in response to epinephrine. Only clones with abundant wild-type c-src protein (greater than 10-fold above endogenous) exhibited enhanced cAMP accumulation, averaging 3.3-fold above control cells. We conclude, therefore, that the enhanced degree of cAMP accumulation in cells overexpressing c-src is dependent upon activation of beta-adrenergic receptors and upon a threshold level of pp60c-src that retains full tyrosine kinase activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propranolol
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Terbutalina
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Epinefrina
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Genes src
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Proteínas Proto-Oncogênicas pp60(c-src)
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AMP Cíclico
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Isoproterenol
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
1990
Tipo de documento:
Article
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA