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Next Article 
The Journal of Neuroscience, January 1, 2002, 22(1):1-9
Protein Kinase Modulation of a Neuronal Cation Channel Requires
Protein-Protein Interactions Mediated by an Src homology 3 Domain
Neil S.
Magoski1,
Gisela F.
Wilson2, and
Leonard K.
Kaczmarek1
1 Department of Pharmacology, Yale University, New
Haven, Connecticut 06520, and 2 Department of Biology,
University of Michigan, Ann Arbor, Michigan 48109
Accumulating evidence suggests that many ion channels reside within
a multiprotein complex that contains kinases and other signaling
molecules. The role of the adaptor proteins that physically link these
complexes together for the purposes of ion channel modulation, however,
has been little explored. Here, we examine the protein-protein
interactions required for regulation of an Aplysia bag
cell neuron cation channel by a closely associated protein
kinase C (PKC). In inside-out patches, the PKC-dependent enhancement of cation channel open probability could be prevented by
the src homology 3 (SH3) domain, presumably by disrupting a link
between the channel and the kinase. SH3 and PDZ domains from other
proteins were ineffective. Modulation was also prevented by an SH3
motif peptide that preferentially binds the SH3 domain of src.
Furthermore, whole-cell depolarizations elicited by cation channel
activation were decreased by the src SH3 domain. These data suggest
that the cation channel-PKC association may require SH3
domain-mediated interactions to bring about modulation, promote membrane depolarization, and initiate prolonged changes in bag cell
neuron excitability. In general, protein-protein interactions between
ion channels and protein kinases may be a prominent mechanism underlying neuromodulation.
Key words:
Aplysia; bag cell neurons; cation channel; phosphorylation; protein kinase C; protein-protein interaction; SH3
domain; excitability.
Copyright © 2002 Society for Neuroscience 0270-6474/02/2211-09$05.00/0
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J. Hannibal, P. Hindersson, J. Ostergaard, B. Georg, S. Heegaard, P. J. Larsen, and J. Fahrenkrug
Melanopsin Is Expressed in PACAP-Containing Retinal Ganglion Cells of the Human Retinohypothalamic Tract
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A. K. Tryba and J.-M. Ramirez
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E. M. Petrini, I. Marchionni, P. Zacchi, W. Sieghart, and E. Cherubini
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L. Marchetti, M. Klein, K. Schlett, K. Pfizenmaier, and U. L. M. Eisel
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D. Ait-Ali, V. Turquier, L. Grumolato, L. Yon, M. Jourdain, D. Alexandre, L. E. Eiden, H. Vaudry, and Y. Anouar
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E. A. Budygin, M. S. Brodie, T. D. Sotnikova, Y. Mateo, C. E. John, M. Cyr, R. R. Gainetdinov, and S. R. Jones
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K. E. Cullen and J. E. Roy
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A. D. Patel and E. Balaban
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B. S. Minnery, R. M. Bruno, and D. J. Simons
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C. J. Quintans, M. J. Donaldson, M. V. Bertolino, and R. S. Pasqualini
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