Epidermal growth factor receptor levels are reduced in mice with targeted disruption of the protein kinase A catalytic subunit.
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, Calpha and Cbeta in two different models. The first model used targeted disruption of either Calpha or Cbeta in mice whereas the second model used Calpha and Cbeta RNA interference in HeLa cells. In both models we observed a significant reduction of EGFR expression at the protein but not mRNA level.


CONCLUSIONS
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.
Oksvold
Morten P
MP
Institute of Pathology, Rikshospitalet University Hospital, University of Oslo, Norway. moroks@rr-research.no
Funderud
Ane
A
Kvissel
Anne-Katrine
AK
Skarpen
Ellen
E
Henanger
Heidi
H
Huitfeldt
Henrik S
HS
Skålhegg
Bjørn S
BS
Ørstavik
Sigurd
S
D000818:Animals; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits