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Platelet-derived growth factor agonist activity of a secreted form of the v-sis oncogene product
Abstract:
We have compared the functional properties of a growth factor partially purified from medium conditioned by simian sarcoma virus-transformed cells with those of platelet-derived growth factor (PDGF). The factor mimicked the effects induced by PDGF: it bound to and activated human fibroblast PDGF receptors and stimulated DNA synthesis. These activities were specifically inhibited by PDGF antibodies and thus elicited by a factor(s) immunologically related to PDGF. The factor behaved as a secretory protein, since about 95% of the receptor-binding activity was found in the medium after a 48-hr serum-free incubation. Structural characterization of the PDGF-like activity revealed a Mr 24,000 intracellular protein and two polypeptides of Mr 13,000 and 11,500 released into the medium. The Mr 13,000 component bound to human fibroblasts; this binding was competitively inhibited by PDGF. The data support the possibility that oncogene products may elicit transforming activity by interacting with the normal cellular mitogenic pathway.
Insights
A simian sarcoma virus-transformed cell growth factor mimics platelet-derived growth factor (PDGF), activating PDGF receptors and stimulating DNA synthesis. This suggests oncogene products may interact with normal cellular pathways for transformation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- Platelet-derived growth factor (PDGF) is a key regulator of cell growth and proliferation.
- Simian sarcoma virus (SSV) transformation is associated with altered cellular signaling pathways.
- Understanding growth factor interactions is crucial for deciphering cellular transformation mechanisms.
Purpose of the Study:
- To compare the functional properties of a growth factor from SSV-transformed cells with PDGF.
- To investigate the interaction of the SSV-derived factor with PDGF receptors.
- To explore the potential role of oncogene products in cellular mitogenic pathways.
Main Methods:
- Partial purification of a growth factor from SSV-transformed cell-conditioned medium.
- Functional assays including receptor binding, activation, and DNA synthesis stimulation in human fibroblasts.
- Immunological inhibition using PDGF antibodies and competitive binding assays.
- Structural characterization of the purified factor using molecular weight determination.
Main Results:
- The SSV-derived growth factor bound to and activated human fibroblast PDGF receptors, mimicking PDGF.
- The factor stimulated DNA synthesis, an effect inhibited by PDGF antibodies, indicating immunological relation to PDGF.
- The factor was identified as a secretory protein, with a Mr 13,000 component binding to fibroblasts and competitively inhibited by PDGF.
Conclusions:
- The growth factor from SSV-transformed cells is immunologically related to PDGF and functionally similar.
- Oncogene products may contribute to cellular transformation by engaging with the normal PDGF-mediated mitogenic pathway.
- This finding provides insight into the molecular mechanisms by which oncogenes can drive cell proliferation and transformation.