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Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase
Abstract
The function of voltage-gated sodium channels that are responsible for action potential generation in mammalian brain neurons is modulated by phosphorylation by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (cA-PK) and by protein kinase C (PKC). Reduction of peak sodium currents by cA-PK in intact cells required concurrent activation of PKC and was prevented by blocking phosphorylation of serine 1506, a site in the inactivation gate of the channel that is phosphorylated by PKC but not by cA-PK. Replacement of serine 1506 with negatively charged amino acids mimicked the effect of phosphorylation. Conversion of the consensus sequence surrounding serine 1506 to one more favorable for cA-PK enhanced modulation of sodium currents by cA-PK. Convergent modulation of sodium channels required phosphorylation of serine 1506 by PKC accompanied by phosphorylation of additional sites by cA-PK. This regulatory mechanism may serve to integrate neuronal signals mediated through these parallel signaling pathways.
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Citations
Cited by
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Catterall, W. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81133-2 · Cited by 2,118
Self-citationLev, S., Moreno, H., Martinez, R., Canoll, P., Peles, E., Musacchio, J. M., Plowman, G. D., Rudy, B., & Schlessinger, J. (1995) · Nature · doi:10.1038/376737a0 · Cited by 1,381
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Mangoni, M. E., & Nargeot, J. (2008) · Physiological Reviews · doi:10.1152/physrev.00018.2007 · Cited by 600
Dib-Hajj, S. D., Tyrrell, L., Black, J. A., & Waxman, S. G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8963 · Cited by 503
Metadata
- Authors
- Li, M., West, J., Numann, R., Murphy, B., Scheuer, T., & Catterall, W.
- Venue
- Science
- Published
- 1993-09-10
- Volume
- 261
- Issue
- 5127
- Pages
- 1439-1442
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2016837051
- Cited by
- 265
- References
- 0
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- closed
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- Li, M., West, J., Numann, R., Murphy, B., Scheuer, T., & Catterall, W. (1993). Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science. https://doi.org/10.1126/science.8396273
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