Linked Life Data

14976207

Source:http://linkedlifedata.com/resource/pubmed/id/14976207

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2004-4-19
pubmed:abstractText
G protein-coupled receptor kinases (GRKs) specifically phosphorylate agonist-occupied G protein-coupled receptors at the inner surface of the plasma membrane (PM), leading to receptor desensitization. GRKs utilize a variety of mechanisms to bind tightly, and sometimes reversibly, to cellular membranes. Previous studies demonstrated the presence of a membrane binding domain in the C terminus of GRK5. Here we define a mechanism by which this short C-terminal stretch of amino acids of GRK5 mediates PM localization. Secondary structure predictions suggest that a region contained within amino acids 546-565 of GRK5 forms an amphipathic helix, with the key features of the predicted helix being a hydrophobic patch of amino acids on one face of the helix, hydrophilic amino acids on the opposite face, and a number of basic amino acids surrounding the hydrophobic patch. We show that amino acids 546-565 of GRK5 are sufficient to target the cytoplasmic green fluorescent protein (GFP) to the PM, and the hydrophobic amino acids are necessary for PM targeting of GFP-546-565. Moreover, full-length GRK5-GFP is localized to the PM, but mutation of the hydrophobic patch or the surrounding basic amino acids prevents PM localization of GRK5-GFP. Last, we show that mutation of the hydrophobic residues severely diminishes phospholipid-dependent autophosphorylation of GRK5 and phosphorylation of membrane-bound rhodopsin by GRK5. The findings in this report thus suggest the presence of a membrane binding motif in GRK5 and define the importance of a group of hydrophobic amino acids within this motif in mediating its PM localization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17989-95
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14976207-Amino Acid Motifs, pubmed-meshheading:14976207-Amino Acid Sequence, pubmed-meshheading:14976207-Animals, pubmed-meshheading:14976207-COS Cells, pubmed-meshheading:14976207-Cell Line, pubmed-meshheading:14976207-Cell Membrane, pubmed-meshheading:14976207-G-Protein-Coupled Receptor Kinase 5, pubmed-meshheading:14976207-Green Fluorescent Proteins, pubmed-meshheading:14976207-Humans, pubmed-meshheading:14976207-Luminescent Proteins, pubmed-meshheading:14976207-Microscopy, Confocal, pubmed-meshheading:14976207-Molecular Sequence Data, pubmed-meshheading:14976207-Mutation, pubmed-meshheading:14976207-Phospholipids, pubmed-meshheading:14976207-Phosphorylation, pubmed-meshheading:14976207-Plasmids, pubmed-meshheading:14976207-Protein Binding, pubmed-meshheading:14976207-Protein Structure, Secondary, pubmed-meshheading:14976207-Protein Structure, Tertiary, pubmed-meshheading:14976207-Protein-Serine-Threonine Kinases, pubmed-meshheading:14976207-Rhodopsin, pubmed-meshheading:14976207-Sequence Homology, Amino Acid, pubmed-meshheading:14976207-Time Factors, pubmed-meshheading:14976207-Tubulin
pubmed:year
2004
pubmed:articleTitle
A predicted amphipathic helix mediates plasma membrane localization of GRK5.
pubmed:affiliation
Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't