Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors
| Autor: | Lewis T. Williams, Shaun R. Coughlin, Patrice Tremble, Jeremy S. Garrett, Gertrude M. Giels, Henry L. Niman |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Platelet-derived growth factor
Genes Viral Oncogene Proteins v-sis Suramin medicine.medical_treatment Receptors Cell Surface Kidney Cell Line Viral Proteins chemistry.chemical_compound medicine Animals Receptors Platelet-Derived Growth Factor Phosphorylation Receptor Autocrine signalling Platelet-Derived Growth Factor Multidisciplinary biology Sarcoma Virus Woolly Monkey Growth factor Tyrosine phosphorylation Oncogenes Protein-Tyrosine Kinases Molecular biology Rats Cell Transformation Neoplastic Retroviridae Genes chemistry biology.protein Protein Kinases Platelet-derived growth factor receptor Research Article medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 81:7466-7470 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.81.23.7466 |
| Popis: | The viral (v)-sis oncogene encodes a protein (p28sis) that is structurally homologous to platelet-derived growth factor (PDGF). We have shown that simian sarcoma virus (SSV)-transformed cells containing the v-sis oncogene release a Mr 20,000 substance that is recognized by antisera to synthetic peptide sequences contained in p28sis. Medium conditioned by SSV-transformed cells competes with 125I-labeled PDGF for specific PDGF receptor sites, initiates DNA synthesis, and stimulates tyrosine phosphorylation of the PDGF receptor when added to normal cells. When normal cells are co-cultured with SSV-transformed cells, the PDGF receptors of the normal cells are down-regulated by factors released from the transformed cells. Thus, SSV-transformed cells release material that is functionally similar to PDGF. We have used anti-phosphotyrosine antibodies to purify PDGF receptors and to detect PDGF-stimulated receptors in normal cells. SSV-transformed cells have no PDGF receptors detectable by these antibodies or by 125I-labeled PDGF binding studies. However, when SSV-transformed cells are exposed to suramin, a compound that blocks binding of PDGF to its receptors, the receptors reappear on the cell surface and within 8 hr are present at the same levels as in control cells. These "new" receptor sites can be phosphorylated in response to PDGF. Thus, the absence of PDGF receptors in SSV-transformed cells is due to down-regulation of the receptors by an autocrine mechanism that can be blocked by suramin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|