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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, B. A. Donoghue, D. J. |
| Description | Author Affiliation: Lee BA ( Department of Biology, University of California, San Diego, La Jolla 92093-0322.) |
| Abstract | An important question regarding autocrine transformation by v-sis is whether intracellularly activated PDGF receptors are sufficient to transform cells or whether activated receptor-ligand complexes are required at the cell surface. We have addressed this question by inhibiting cell surface transport of a membrane-anchored v-sis protein utilizing the ER retention signal of the adenoviral transmembrane protein E3/19K. A v-sis fusion protein containing this signal was retained within the cell and not transported to the cell surface as confirmed by immunofluorescent localization experiments. Also, proteolytic maturation of this protein was suppressed, indicating inefficient transport to post-Golgi compartments of the secretory pathway. When compared with v-sis proteins lacking a functional retention signal, the ER-retained protein showed a diminished ability to transform NIH 3T3 cells, as measured by the number and size of foci formed. In newly established cell lines, the ER-retained protein did not down-regulate PDGF receptors. However, continued passage of these cells selected for a fully transformed phenotype exhibiting downregulated PDGF receptors and proteolytically processed v-sis protein. These results indicate that productive autocrine interactions occur in a post-ER compartment of the secretory pathway. Transport of v- sis protein beyond the Golgi correlated with acquisition of the transformed phenotype. Furthermore, suramin treatment reversed transformation and upregulated the expression of cell surface PDGF receptors, suggesting an important role for receptor-ligand complexes localized to the cell surface. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 118 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1992-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Membrane Metabolism Cell Transformation, Neoplastic Endoplasmic Reticulum Retroviridae Proteins, Oncogenic Signal Transduction 3T3 Cells Amino Acid Sequence Animals Drug Effects Down-Regulation Golgi Apparatus Mice Molecular Sequence Data Oncogene Proteins V-sis Receptors, Cell Surface Receptors, Platelet-Derived Growth Factor Sarcoma Virus, Woolly Monkey Suramin Pharmacology Up-Regulation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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