PMID- 12596920
OWN - NLM
STAT- MEDLINE
DCOM- 20030723
LR  - 20190622
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 514
DP  - 2002
TI  - Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit 
      (Pgamma) of retinal cgmp phosphodiesterase (PDE6): its implications in 
      phototransduction.
PG  - 131-53
AB  - Cyclic GMP phosphodiesterase (PDE6) is a key enzyme in vertebrate retinal 
      phototransduction. After GTP/GDP exchange on the a subunit of transducin (Talpha) 
      by illuminated rhodopsin, the GTP-bound form Talpha (GTP/Talpha) interacts with 
      the regulatory subunit (Pgamma) 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 Pgamma complexed with GTP/Talpha in vitro and in vivo. 
      Phosphorylated Py dissociates from GTP/Talpha 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 Pgamma 
      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.
FAU - Yamazaki, Akio
AU  - Yamazaki A
AD  - Department of Ophthalmology, Kresge Eye Institute, Wayne State University, School 
      of Medicine, Detroit, Michigan 48201, USA.
FAU - Moskvin, Oleg
AU  - Moskvin O
FAU - Yamazaki, Russell K
AU  - Yamazaki RK
LA  - eng
GR  - EY07546/EY/NEI NIH HHS/United States
GR  - EY09631/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (CDK5 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 6)
RN  - EC 3.1.4.35 (PDE6B protein, human)
SB  - IM
MH  - Amino Acid Motifs
MH  - Animals
MH  - Cyclic Nucleotide Phosphodiesterases, Type 6
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Hydrolysis
MH  - Models, Biological
MH  - Phosphoric Diester Hydrolases/*chemistry/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Retina/*metabolism
RF  - 77
EDAT- 2003/02/25 04:00
MHDA- 2003/07/24 05:00
CRDT- 2003/02/25 04:00
PHST- 2003/02/25 04:00 [pubmed]
PHST- 2003/07/24 05:00 [medline]
PHST- 2003/02/25 04:00 [entrez]
AID - 10.1007/978-1-4615-0121-3_9 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2002;514:131-53. doi: 10.1007/978-1-4615-0121-3_9.