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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Liu, W. W. Garrison, J. C. Mattingly, R. R. |
| Description | Author Affiliation: Liu WW ( Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville 22908, USA.); |
| Abstract | Two major intermediaries in signal transduction pathways are pp60v-sre family tyrosine kinases and heterotrimeric guanine nucleotide-binding proteins. In Rat-1 fibroblasts transformed by the v-src oncogene, endothelin-1 (ET-1)-induced inositol 1,4,5-trisphosphate accumulation is increased 6-fold, without any increases in the numbers of ET-1 receptors or in the response to another agonist, thrombin. This ET-1 hyperresponse can be inhibited by an antibody directed against the carboxyl terminus of the Gq/G11 alpha subunit, suggesting that the Gq/G11 protein couples ET-1 receptors to phospholipase C (PLC). While v-src transformation did not increase the expression of the Gq/G11 alpha subunit, immunoblotting with anti-phosphotyrosine antibodies and phosphoamino acid analysis demonstrated that the Gq/G11 alpha subunit becomes phosphorylated on tyrosine residues in v-src-transformed cells. Moreover, when the Gq/G11 protein was extracted from control and transformed cell lines and reconstituted with exogenous PLC, AIF*4-stimulated Gq/G11 activity was markedly increased in extracts from v-src-transformed cells. Our results demonstrate that the process of v-src transformation can increase the tyrosine phosphorylation state of the Gq/G11 alpha-subunit in intact cells and that the process causes an increase in the Gq/G11 alpha-subunit's ability to stimulate PLC following activation with AIF-4. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Transformation, Neoplastic Metabolism GTP-Binding Proteins Genes, Src Oncogene Protein Pp60(v-src) Protein-Tyrosine Kinases Receptors, Endothelin Physiology Receptors, Thrombin Animals Cells, Cultured Phosphotyrosine Receptor, Endothelin A Signal Transduction Type C Phospholipases Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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