Simultaneous binding of two protein kinases to a calcium-dependent potassium channel.

J. Wang, Y. Zhou, Hua Wen, I. B. Levitan

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Large-conductance calcium-dependent potassium channels are subject to modulation by protein kinases, phosphatases, and other signaling proteins, and it has been inferred from electrophysiological experiments that signaling proteins sometimes can be intimately associated with these channels in a regulatory complex. We show here that endogenous protein kinase activity coimmunoprecipitates with both native and recombinant Drosophila Slowpoke (dSlo) calcium-dependent potassium channels. Coimmunoprecipitation experiments using antibodies against several protein kinases demonstrate that dSlo can bind simultaneously to the Src tyrosine kinase and to the catalytic subunit of the cAMP-dependent protein kinase (PKAc). Both kinases can phosphorylate the channel in Drosophila heads and in heterologous host cells. The PKAc binds directly to a 172-amino acid region in the C-terminal domain of dSlo, without the intervention of regulatory subunits or anchoring proteins, and channel phosphorylation by PKAc is not required for this binding interaction. In contrast, several phosphorylatable tyrosine residues in dSlo are important for Src binding. The results are consistent with the idea that an ion channel can act as a scaffold for its own specific set of modulatory enzymes.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume19
Issue number10
StatePublished - 1999
Externally publishedYes

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Calcium-Activated Potassium Channels
Protein Kinases
Drosophila
Carrier Proteins
Proteins
src-Family Kinases
Phosphoprotein Phosphatases
Cyclic AMP-Dependent Protein Kinases
Ion Channels
Tyrosine
Catalytic Domain
Phosphotransferases
Head
Phosphorylation
Amino Acids
Antibodies
Enzymes

Cite this

Simultaneous binding of two protein kinases to a calcium-dependent potassium channel. / Wang, J.; Zhou, Y.; Wen, Hua; Levitan, I. B.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 19, No. 10, 1999.

Research output: Contribution to journalArticle

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