RGD Reference Report - Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin. - Rat Genome Database

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Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin.

Authors: Hattan, D  Nesti, E  Cachero, TG  Morielli, AD 
Citation: Hattan D, etal., J Biol Chem. 2002 Oct 11;277(41):38596-606. Epub 2002 Jul 31.
RGD ID: 10047206
Pubmed: PMID:12151401   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M205005200   (Journal Full-text)

Tyrosine phosphorylation evokes functional changes in a variety of ion channels. Modulation of the actin cytoskeleton also affects the function of some channels. Little is known about how these avenues of ion channel regulation may interact. We report that the potassium channel Kv1.2 associates with the actin-binding protein cortactin and that the binding is modulated by tyrosine phosphorylation. Immunocytochemical and biochemical analyses show that Kv1.2 and cortactin co-localize to the cortical actin cytoskeleton at the leading edges of the cell. Binding assays using purified recombinant proteins reveal a 19-amino acid span within the carboxyl terminus of Kv1.2 that is necessary for direct cortactin binding. Phosphorylation of specific tyrosines within the C terminus of Kv1.2 attenuates that binding. In HEK293 cells, activation of the M1 muscarinic acetylcholine receptor evokes tyrosine phosphorylation-dependent suppression of Kv1.2 ionic current. We show that M1 receptor activation also reduces the interaction of cortactin with Kv1.2 and that mutant Kv1.2 channels deficient for cortactin binding exhibit strongly attenuated ionic current. These results demonstrate a dynamic, phosphorylation-dependent interaction between Kv1.2 and the actin cytoskeleton-binding protein cortactin and suggest a role for that interaction in the regulation of Kv1.2 ionic current.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lamellipodium located_inIDA 10047206PMID:12151401UniProt 
voltage-gated potassium channel complex located_inIDA 10047206PMID:12151401UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Cttn  (cortactin)
Kcna2  (potassium voltage-gated channel subfamily A member 2)


Additional Information