Article: Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase
File Download
Links for fulltext
(May Require Subscription)
(May Require Subscription)
- Publisher Website: 10.1016/j.bbamcr.2011.10.010
- Scopus: eid_2-s2.0-84862802638
- PMID: 22061963
- Find via
Supplementary
-
Citations:
-
Appears in Collections:
| Title | Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Wu, W1 Dong, MQ1 Wu, XG1 Sun, HY1 Tse, HF1 Lau, CP1 Li, GR1 | ||||||
| Keywords | EGFR kinase Ion channel modulation Protein tyrosine kinase Protein tyrosine phosphorylation Signal transduction | ||||||
| Issue Date | 2012 | ||||||
| Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbamcr | ||||||
| Citation | Biochimica Et Biophysica Acta - Molecular Cell Research, 2012, v. 1823 n. 2, p. 282-289 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bbamcr.2011.10.010 | ||||||
| Abstract | Human ether á-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10μM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10μM) or the Src-family inhibitor PP2 (10μM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr 90, Try 344, and Try 485. This effect is likely involved in regulating neuronal activity and/or tumor growth. © 2011 Elsevier B.V. | ||||||
| ISSN | 0167-4889 2011 Impact Factor: 5.538 2011 SCImago Journal Rankings: 0.707 | ||||||
| DOI | http://dx.doi.org/10.1016/j.bbamcr.2011.10.010 | ||||||
| ISI Accession Number ID | WOS:000301155700010
Funding Information: The study was supported in part by a Small Project Fund (201007176213) of the University of Hong Kong and by Sun Chieh Yeh Heart Foundation of Hong Kong. Wei Wu is supported by a postgraduate studentship from the University of Hong Kong. Ming-Qing Dong is supported by a postdoctoral fellowship of the University of Hong Kong. The authors thank Dr. L Pardo, Max Planck Institute of Experimental Medicine, Gottingen, Germany, for generously providing us with the hEAG1/pTracer CMV plasmid. | ||||||
| References | References in Scopus | ||||||
| Grants | Regulation of human ether-\x85-go-go gene K+ channels by EGFR kinase |
| dc.contributor.author | Wu, W | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Dong, MQ | ||||||
| dc.contributor.author | Wu, XG | ||||||
| dc.contributor.author | Sun, HY | ||||||
| dc.contributor.author | Tse, HF | ||||||
| dc.contributor.author | Lau, CP | ||||||
| dc.contributor.author | Li, GR | ||||||
| dc.date.accessioned | 2011-11-24T10:04:13Z | ||||||
| dc.date.available | 2011-11-24T10:04:13Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.abstract | Human ether á-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10μM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10μM) or the Src-family inhibitor PP2 (10μM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr 90, Try 344, and Try 485. This effect is likely involved in regulating neuronal activity and/or tumor growth. © 2011 Elsevier B.V. | ||||||
| dc.description.grant | Regulation of human ether-\x85-go-go gene K+ channels by EGFR kinase | ||||||
| dc.description.grantcode | 104077 | ||||||
| dc.description.nature | postprint | ||||||
| dc.identifier.citation | Biochimica Et Biophysica Acta - Molecular Cell Research, 2012, v. 1823 n. 2, p. 282-289 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bbamcr.2011.10.010 | ||||||
| dc.identifier.citeulike | 9967806 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.bbamcr.2011.10.010 | ||||||
| dc.identifier.epage | 289 | ||||||
| dc.identifier.hkuros | 197775 | ||||||
| dc.identifier.hkuros | 199747 | ||||||
| dc.identifier.isi | WOS:000301155700010
Funding Information: The study was supported in part by a Small Project Fund (201007176213) of the University of Hong Kong and by Sun Chieh Yeh Heart Foundation of Hong Kong. Wei Wu is supported by a postgraduate studentship from the University of Hong Kong. Ming-Qing Dong is supported by a postdoctoral fellowship of the University of Hong Kong. The authors thank Dr. L Pardo, Max Planck Institute of Experimental Medicine, Gottingen, Germany, for generously providing us with the hEAG1/pTracer CMV plasmid. | ||||||
| dc.identifier.issn | 0167-4889 2011 Impact Factor: 5.538 2011 SCImago Journal Rankings: 0.707 | ||||||
| dc.identifier.issue | 2 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 22061963 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84862802638 | ||||||
| dc.identifier.spage | 282 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/143374 | ||||||
| dc.identifier.volume | 1823 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbamcr | ||||||
| dc.publisher.place | Netherlands | ||||||
| dc.relation.ispartof | Biochimica et Biophysica Acta - Molecular Cell Research | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta, 2012, v. 1823 n. 2, p. 282-289. DOI: 10.1016/j.bbamcr.2011.10.010 | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject | EGFR kinase | ||||||
| dc.subject | Ion channel modulation | ||||||
| dc.subject | Protein tyrosine kinase | ||||||
| dc.subject | Protein tyrosine phosphorylation | ||||||
| dc.subject | Signal transduction | ||||||
| dc.title | Human ether-à-go-go gene potassium channels are regulated by EGFR tyrosine kinase | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine