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| Content Provider | PubMed Central |
|---|---|
| Author | Bushman, W. A. Wilson, L. K. Luttrell, D. K. Moyers, J. S. Parsons, S. J. |
| 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. |
| Starting Page | 7462 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 87 |
| Language | English |
| Publisher Date | 1990-10-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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