RGD Reference Report - Regulation of an ERG K+ current by Src tyrosine kinase. - Rat Genome Database

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Regulation of an ERG K+ current by Src tyrosine kinase.

Authors: Cayabyab, FS  Schlichter, LC 
Citation: Cayabyab FS and Schlichter LC, J Biol Chem 2002 Apr 19;277(16):13673-81.
RGD ID: 634207
Pubmed: PMID:11834728   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M108211200   (Journal Full-text)

The human "ether-a-go-go"-related gene (HERG) K(+) channel, and its homologues are present in heart, neuronal tissue, some cancer cells, and the MLS-9 rat microglia cell line (Zhou, W., Cayabyab, F. S., Pennefather, P. S., Schlichter, L. C., and DeCoursey, T. E. (1998) J. Gen. Physiol. 111, 781-794). Despite its importance, there are few studies of ERG modulation. In this first report of regulation by tyrosine phosphorylation we show that MLS-9 cells express transcripts for r-erg1 (rat homologue of HERG) and r-erg2, and an immunoreactive doublet was identified using an anti-HERG antibody. The constitutive tyrosine phosphorylation of the ERG1 protein, detected by co-immunoprecipitation, was reduced by the protein-tyrosine kinase inhibitors, lavendustin A, herbimycin A, or genistein (but not daidzein). The whole cell ERG current was reduced by protein-tyrosine kinase inhibitors or the Src-selective inhibitory peptide, src40-58, but not by a scrambled peptide. Conversely, the current was increased by the Src-activating peptide, srcpY, but not by an inactive analogue. Activating endogenous Src or transfecting constitutively active v-Src altered the voltage dependence and deactivation kinetics to produce more current at negative potentials. Co-immunoprecipitation identified an association between the channel protein and Src. Thus, r-ERG1 and Src tyrosine kinase appear to exist in a signaling complex that is well positioned to modulate this K(+) channel and affect its contribution to cellular functions.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPISrc (Rattus norvegicus)634207 RGD 
transmembrane transporter binding  IPIHsf2 (Rattus norvegicus)634207 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kcnh1  (potassium voltage-gated channel subfamily H member 1)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)

Objects referenced in this article
Gene Kcnh2 potassium voltage-gated channel subfamily H member 2 Rattus norvegicus

Additional Information