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Conference Paper: Molecular mechanism for the modulation of human ether á-go-go gene potassium channels by EGFR tyrosine kinase

TitleMolecular mechanism for the modulation of human ether á-go-go gene potassium channels by EGFR tyrosine kinase
Authors
Issue Date2009
PublisherHong Kong Academy of Medicine
Citation
14th Medical Research Conference, Hong Kong, 10 January 2009. In Hong Kong Medical Journal, 2009, v. 15 n. S1, p. 37 How to Cite?
AbstractIntroduction: Human ether á-go-go gene potassium channels (hEAG1) are expressed in brain and several types of human cancers, and play a critical role in neuronal excitement and tumour progression. However, functional regulation of hEAG channels is not understood. The present study was designed to determine whether hEAG1 channels are regulated by epidermal growth factor receptor (EGFR) kinase. Methods: The hEAG1 current was recorded in HEK 293 stably expressing hEAG1 gene with a whole-cell patch clamp technique. Mutants of hEAG1 channels were generated using site-directed mutagenesis. Results: It was found that AG556, a highly selective inhibitor of EGFR kinase, suppressed hEAG1 current in a concentration-dependent manner. The inhibitory effect was fully antagonised by co-application of AG556 and orthovanadate (1 mM, inhibitor of protein tyrosine phosphatases). In addition, EGF (100 ng/mL) slightly increased hEAG1 current in cells with a 36-hour starvation. In mutants of hEAG1 channels, the inhibitory effect of hEAG1 current by AG556 was largely attenuated for hEAG1-Y90A, Y344A and Y485A, but not for hEAG1-Y376A, Y479A and Y639F. Conclusion: Our results demonstrate for the first that EGFR kinase modulates hEAG1 channel activity via phosphorylating tyrosine residues (Tyr90, Try344 and Try485) and therefore likely regulates neuronal activity and tumour growth. Acknowledgement: This research was supported by Sun Chieh Yeh Heart Foundation.
Persistent Identifierhttp://hdl.handle.net/10722/62434
ISSN
2015 Impact Factor: 0.887
2015 SCImago Journal Rankings: 0.279

 

DC FieldValueLanguage
dc.contributor.authorWu, Wen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2010-07-13T04:01:08Z-
dc.date.available2010-07-13T04:01:08Z-
dc.date.issued2009en_HK
dc.identifier.citation14th Medical Research Conference, Hong Kong, 10 January 2009. In Hong Kong Medical Journal, 2009, v. 15 n. S1, p. 37-
dc.identifier.issn1024-2708-
dc.identifier.urihttp://hdl.handle.net/10722/62434-
dc.description.abstractIntroduction: Human ether á-go-go gene potassium channels (hEAG1) are expressed in brain and several types of human cancers, and play a critical role in neuronal excitement and tumour progression. However, functional regulation of hEAG channels is not understood. The present study was designed to determine whether hEAG1 channels are regulated by epidermal growth factor receptor (EGFR) kinase. Methods: The hEAG1 current was recorded in HEK 293 stably expressing hEAG1 gene with a whole-cell patch clamp technique. Mutants of hEAG1 channels were generated using site-directed mutagenesis. Results: It was found that AG556, a highly selective inhibitor of EGFR kinase, suppressed hEAG1 current in a concentration-dependent manner. The inhibitory effect was fully antagonised by co-application of AG556 and orthovanadate (1 mM, inhibitor of protein tyrosine phosphatases). In addition, EGF (100 ng/mL) slightly increased hEAG1 current in cells with a 36-hour starvation. In mutants of hEAG1 channels, the inhibitory effect of hEAG1 current by AG556 was largely attenuated for hEAG1-Y90A, Y344A and Y485A, but not for hEAG1-Y376A, Y479A and Y639F. Conclusion: Our results demonstrate for the first that EGFR kinase modulates hEAG1 channel activity via phosphorylating tyrosine residues (Tyr90, Try344 and Try485) and therefore likely regulates neuronal activity and tumour growth. Acknowledgement: This research was supported by Sun Chieh Yeh Heart Foundation.-
dc.languageengen_HK
dc.publisherHong Kong Academy of Medicine-
dc.relation.ispartofHong Kong Medical Journal-
dc.titleMolecular mechanism for the modulation of human ether á-go-go gene potassium channels by EGFR tyrosine kinaseen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLau, CP: cplau@hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.identifier.hkuros154270en_HK

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