Related Experiment Videos
Growth factors modify the epidermal growth factor receptor through multiple pathways
Abstract:
Previous results have shown that tumor promoters modify the properties of the epidermal growth factor (EGF) receptor through the activation of protein kinase C. Diacylglycerol-generating factors such as platelet-derived growth factor (PDGF) and p28sis should activate protein kinase C and alter EGF receptor properties in a similar manner. To test directly the involvement of protein kinase C in the action of media from v-sis-transformed cells on the EGF receptor, Swiss 3T3 cells were first extensively treated with various concentrations of the tumor-promoter phorbol dibutyrate (PDBu) This treatment reduced levels of active protein kinase C in the cells, making them less responsive to subsequent rechallenge with the tumor promoter. The results demonstrate that there are at least two components to the action of media from v-sis transformed cells on EGF binding: a labile factor that confers protein kinase C independence and a stable factor that appears to be dependent on protein kinase C. The action of the first factor cannot be mimicked by transforming growth factor-beta or EGF in either the presence or absence of PDGF. The action of the second factor is similar to that of PDGF. These findings indicate that heterologous regulation of the EGF receptor can occur through both protein kinase C-dependent and -independent pathways.
Insights
Tumor promoters alter epidermal growth factor (EGF) receptor properties via protein kinase C. This study reveals two factors in v-sis transformed cells affecting EGF binding, one dependent and one independent of protein kinase C.
Area of Science:
- Cell Biology
- Molecular Oncology
- Signal Transduction
Background:
- Tumor promoters modulate epidermal growth factor (EGF) receptor activity through protein kinase C (PKC) activation.
- Platelet-derived growth factor (PDGF) and p28sis are diacylglycerol-generating factors expected to activate PKC and influence EGF receptor properties.
Purpose of the Study:
- To investigate the direct involvement of PKC in the effects of v-sis-transformed cell media on the EGF receptor.
- To differentiate between PKC-dependent and -independent mechanisms regulating EGF receptor function.
Main Methods:
- Swiss 3T3 cells were pre-treated with phorbol dibutyrate (PDBu) to reduce active PKC levels, assessing subsequent responsiveness.
- Analysis of EGF receptor binding properties in response to media from v-sis-transformed cells under varying conditions.
Main Results:
- Media from v-sis-transformed cells exhibit two components affecting EGF binding: a PKC-independent labile factor and a PKC-dependent stable factor.
- The PKC-independent factor's action was not mimicked by TGF-β or EGF, with or without PDGF.
- The PKC-dependent factor's action resembled that of PDGF.
Conclusions:
- Heterologous regulation of the EGF receptor involves both PKC-dependent and PKC-independent signaling pathways.
- V-sis-transformed cells release factors that differentially modulate EGF receptor activity through distinct mechanisms.