Epidermal growth factor receptor levels are reduced in mice with targeted disruption of the protein kinase A catalytic subunit
| Autor: | Ellen Skarpen, Anne-Katrine Kvissel, Heidi Hatledal Henanger, Bjørn Steen Skålhegg, Ane Funderud, Henrik S. Huitfeldt, Sigurd Ørstavik, Morten P. Oksvold |
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| Rok vydání: | 2007 |
| Předmět: |
Protein subunit
Down-Regulation Mitogen-activated protein kinase kinase Biology Tropomyosin receptor kinase C Gene Expression Regulation Enzymologic Mice Growth factor receptor Epidermal growth factor Animals Humans ASK1 ERBB3 RNA Messenger lcsh:QH573-671 Protein kinase A Mice Knockout Cyclic AMP-Dependent Protein Kinase Catalytic Subunits Epidermal Growth Factor lcsh:Cytology Cell Biology Molecular biology Cell biology ErbB Receptors RNA Interference HeLa Cells Signal Transduction Research Article |
| Zdroj: | BMC Cell Biology BMC Cell Biology, Vol 9, Iss 1, p 16 (2008) |
| ISSN: | 1471-2121 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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