Research article

Epidermal growth factor receptor levels are reduced in mice with targeted disruption of the protein kinase A catalytic subunit

Morten P Oksvold¹ , Ane Funderud² , Anne-Katrine Kvissel² , Ellen Skarpen¹ , Heidi Henanger² , Henrik S Huitfeldt¹ , Bjørn S Skålhegg² and Sigurd Ørstavik²

¹Institute of Pathology, Rikshospitalet University Hospital, University of Oslo, Norway

²Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo Medical School, Norway

author email corresponding author email

BMC Cell Biology 2008, 9:16doi:10.1186/1471-2121-9-16

Published:	1 April 2008

Abstract

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.