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Phosphorylation by Cyclin-Dependent Protein Kinase 5 Of The Regulatory Subunit (Pγ) Of Retinal cGMP Phosphodiesterase (PDE6): Its Implications In Phototransduction

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Photoreceptors and Calcium

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 514))

Abstract

Cyclic GMP phosphodiesterase (PDE6) is a key enzyme in vertebrate retinal phototransduction. After GTP/GDP exchange on the a subunit of transducin (Ta) by illuminated rhodopsin, the GTP-bound form Ta (GTP/Ta) interacts with the regulatory subunit (Py) of PDE6 to activate cGMP hydrolytic activity. The regulatory mechanism of PDE6 has been believed to be a typical G protein-mediated signal transduction process. We found that cyclin-dependent protein kinase 5 (Cdk5) phosphorylates Py complexed with GTP/Ta in vitro and in vivo. Phosphorylated Py dissociates from GTP/Ta without GTP hydrolysis and interacts effectively with catalytic subunits of PDE6 to inhibit the enzyme activity. These observations provide new twists to the current model of retinal phototransduction. In this article, in addition to the details of Py phosphorylation by Cdk5, we review previous studies implying the Py phosphorylation and the turnoff of PDE6 without GTP hydrolysis and indicate the direction for future studies of Py phosphorylation, including the possible involvement of Ca2+/Ca2+-binding proteins.

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Authors and Affiliations

  1. Departments of Ophthalmology, The Kresge Eye Institute, Wayne State University, School of Medicine, Detroit, Michigan, 48201, USA

    Akio Yamazaki & Oleg Moskvin

  2. Departments of Pharmacology, School of Medicine, Detroit, Michigan, 48201, USA

    Akio Yamazaki & Russell K. Yamazaki

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  1. Akio Yamazaki
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  2. Oleg Moskvin
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  3. Russell K. Yamazaki
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Editors and Affiliations

  1. Moran Eye Center/EIHG, University of Utah Health Science Center, 15 North/ 2030 East, Salt Lake City, UT, 84112-5330, USA

    Wolfgang Baehr Ph.D.

  2. Department of Ophthalmology, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA

    Krzysztof Palczewski Ph.D.

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Yamazaki, A., Moskvin, O., Yamazaki, R.K. (2002). Phosphorylation by Cyclin-Dependent Protein Kinase 5 Of The Regulatory Subunit (Pγ) Of Retinal cGMP Phosphodiesterase (PDE6): Its Implications In Phototransduction. In: Baehr, W., Palczewski, K. (eds) Photoreceptors and Calcium. Advances in Experimental Medicine and Biology, vol 514. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0121-3_9

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  • DOI: https://doi.org/10.1007/978-1-4615-0121-3_9

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