Modulation of the G Protein Regulator Phosducin by Ca 2+/Calmodulin-dependent Protein Kinase II Phosphorylation and 14-3-3 Protein Binding

Craig D. Thulin, Justin R. Savage, Joseph N. McLaughlin, Steven M. Truscott, William M. Old, Natalie G. Ahn, Katheryn A. Resing, Heidi E. Hamm, Mark W. Bitensky, Barry M. Willardson

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51 Scopus citations

Abstract

Phototransduction is a canonical G protein-mediated cascade of retinal photoreceptor cells that transforms photons into neural responses. Phosducin (Pd) is a Gβγ-binding protein that is highly expressed in photoreceptors. Pd is phosphorylated in dark-adapted retina and is dephosphorylated in response to light. Dephosphorylated Pd binds Gβγ with high affinity and inhibits the interaction of Gβγ with Gα or other effectors, whereas phosphorylated Pd does not. These results have led to the hypothesis that Pd down-regulates the light response. Consequently, it is important to understand the mechanisms of regulation of Pd phosphorylation. We have previously shown that phosphorylation of Pd by cAMP-dependent protein kinase moderately inhibits its association with Gβγ. In this study, we report that Pd was rapidly phosphorylated by Ca 2+/calmodulin-dependent kinase II, resulting in 100-fold greater inhibition of Gβγ binding than cAMP-dependent protein kinase phosphorylation. Furthermore, Pd phosphorylation by Ca 2+/calmodulin-dependent kinase II at Ser-54 and Ser-73 led to binding of the phosphoserine-binding protein 14-3-3. Importantly, in vivo decreases in Ca2+ concentration blocked the interaction of Pd with 14-3-3, indicating that Ca2+ controls the phosphorylation state of Ser-54 and Ser-73 in vivo. These results are consistent with a role for Pd in Ca2+-dependent light adaptation processes in photoreceptor cells and also suggest other possible physiological functions.

Original languageEnglish (US)
Pages (from-to)23805-23815
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number26
DOIs
StatePublished - Jun 29 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Thulin, C. D., Savage, J. R., McLaughlin, J. N., Truscott, S. M., Old, W. M., Ahn, N. G., Resing, K. A., Hamm, H. E., Bitensky, M. W., & Willardson, B. M. (2001). Modulation of the G Protein Regulator Phosducin by Ca 2+/Calmodulin-dependent Protein Kinase II Phosphorylation and 14-3-3 Protein Binding. Journal of Biological Chemistry, 276(26), 23805-23815. https://doi.org/10.1074/jbc.M101482200