Epidermal growth factor receptor levels are reduced in mice with targeted disruption of the protein kinase A catalytic subunit
✍ Scribed by Morten P Oksvold; Ane Funderud; Anne-Katrine Kvissel; Ellen Skarpen; Heidi Henanger; Henrik S Huitfeldt; Bjørn S Skålhegg; Sigurd Ørstavik
- Publisher
- BioMed Central
- Year
- 2008
- Tongue
- English
- Weight
- 818 KB
- Volume
- 9
- Category
- Article
- ISSN
- 1471-2121
No coin nor oath required. For personal study only.
✦ Synopsis
Background
Epidermal Growth Factor Receptor (EGFR) is a key target molecule in current treatment of several neoplastic diseases. Hence, in order to develop and improve current drugs targeting EGFR signalling, an accurate understanding of how this signalling pathway is regulated is required. It has recently been demonstrated that inhibition of cAMP-dependent protein kinase (PKA) induces a ligand-independent internalization of EGFR. Cyclic-AMP-dependent protein kinase consists of a regulatory dimer bound to two catalytic subunits.
Results
We have investigated the effect on EGFR levels after ablating the two catalytic subunits, Cα and Cβ in two different models. The first model used targeted disruption of either Cα or Cβ in mice whereas the second model used Cα and Cβ RNA interference in HeLa cells. In both models we observed a significant reduction of EGFR expression at the protein but not mRNA level.
Conclusion
Our results suggest that PKA may represent a target that when manipulated can maintain EGFR protein levels at the single cell level as well as in intact animals.