EXPRESSION OF VOLTAGE-GATED POTASSIUM CHANNELS DECREASES CELLULAR PROTEIN-TYROSINE PHOSPHORYLATION

Protein tyrosine phosphorylation by endogenous and expressed tyrosine kinases is reduced markedly by the expression of functional voltage-ga ted potassium (Kv) channels. The levels of tyrosine kinase protein and cellular protein substrates are unaffected, consistent with a reducti on in tyrosine phosphorylation that results from inhibition of protein tyrosine kinase activity. The attenuation of protein tyrosine phospho rylation is correlated with the gating properties of expressed wild-ty pe and mutant Ky channels. Furthermore, cellular protein tyrosine phos phorylation is reduced within minutes by acute treatment with the elec trogenic potassium ionophore valinomycin. Because tyrosine phosphoryla tion in turn influences Ky channel activity, these results suggest tha t reciprocal modulatory interactions occur between Kv channel and prot ein tyrosine phosphorylation signaling pathways.