Linked Life Data

11601986

Source:http://linkedlifedata.com/resource/pubmed/id/11601986

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2001-10-16
pubmed:abstractText
In vertebrate photoreceptors, photoexcited rhodopsin interacts with the G protein transducin, causing it to bind GTP and stimulate the enzyme cGMP phosphodiesterase. The rapid termination of the active state of this pathway is dependent upon a photoreceptor-specific regulator of G protein signaling RGS9-1 that serves as a GTPase activating protein (GAP) for transducin. Here, we show that, in preparations of photoreceptor outer segments (OS), RGS9-1 is readily phosphorylated by an endogenous Ser/Thr protein kinase. Protein kinase C and MAP kinase inhibitors reduced labeling by about 30%, while CDK5 and CaMK II inhibitors had no effect. cAMP-dependent protein kinase (PKA) inhibitor H89 reduced RGS9-1 labeling by more than 90%, while dibutyryl-cAMP stimulated it 3-fold, implicating PKA as the major kinase responsible for RGS9-1 phosphorylation in OS. RGS9-1 belongs to an RGS subfamily also including RGS6, RGS7, and RGS11, which exist as heterodimers with the G protein beta subunit Gbeta5. Phosphorylated RGS9-1 remains associated with Gbeta5L, a photoreceptor-specific splice form, which itself was not phosphorylated. RGS9-1 immunoprecipitated from OS was in vitro phosphorylated by exogenous PKA. The PKA catalytic subunit could also phosphorylate recombinant RGS9-1, and mutational analysis localized phosphorylation sites to Ser(427) and Ser(428). Substitution of these residues for Glu, to mimic phosphorylation, resulted in a reduction of the GAP activity of RGS9-1. In OS, RGS9-1 phosphorylation required the presence of free Ca(2+) ions and was inhibited by light, suggesting that RGS9-1 phosphorylation could be one of the mechanisms mediating a stronger photoresponse in dark-adapted cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12619-27
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11601986-Amino Acid Sequence, pubmed-meshheading:11601986-Animals, pubmed-meshheading:11601986-Calcium, pubmed-meshheading:11601986-Cattle, pubmed-meshheading:11601986-Chelating Agents, pubmed-meshheading:11601986-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:11601986-Egtazic Acid, pubmed-meshheading:11601986-GTP-Binding Proteins, pubmed-meshheading:11601986-GTPase-Activating Proteins, pubmed-meshheading:11601986-Light, pubmed-meshheading:11601986-Molecular Sequence Data, pubmed-meshheading:11601986-Mutagenesis, Site-Directed, pubmed-meshheading:11601986-Phosphorylation, pubmed-meshheading:11601986-Photoreceptor Cells, Vertebrate, pubmed-meshheading:11601986-RGS Proteins, pubmed-meshheading:11601986-Rod Cell Outer Segment, pubmed-meshheading:11601986-Serine, pubmed-meshheading:11601986-Vision, Ocular
pubmed:year
2001
pubmed:articleTitle
Phosphorylation of the regulator of G protein signaling RGS9-1 by protein kinase A is a potential mechanism of light- and Ca2+-mediated regulation of G protein function in photoreceptors.
pubmed:affiliation
Department of Molecular and Cellular Pharmacology and Neuroscience Program, University of Miami School of Medicine, Miami, Florida 33136, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't