Linked Life Data

9733722

Source:http://linkedlifedata.com/resource/pubmed/id/9733722

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
1998-10-15
pubmed:abstractText
We have previously shown that the rat follitropin receptor (rFSHR) expressed in transfected cells becomes phosphorylated upon stimulation of the cells with agonist or a phorbol ester. Peptide mapping and mutagenesis studies have also shown that the agonist- or phorbol ester-induced phosphorylation of the rFSHR maps to Ser/Thr residues present in the first and third intracellular loops. The experiments presented herein were initially designed to test for the presence of additional phosphorylation sites on the second intracellular loop of the rFSHR. Analysis of two new mutants in which the two threonines in the second intracellular loop (rFSHR-2L) or the two threonines in the second intracellular loop and the seven Ser/Thr residues in the third intracellular loop (rFSHR-2L + 3L) were mutated showed that one or more of the two threonines in the second intracellular loop are phosphorylated in response to phorbol ester, but not in response to agonist stimulation. Since rFSHR-2L and rFSHR-2L + 3L displayed a reduction in agonist-induced signaling, two additional mutants (rFSHR-D389N and rFSHR-Y530F) were constructed in an attempt to better understand the relationship between the agonist-induced activation, phosphorylation, and internalization of the rFSHR. These point mutations impaired agonist-stimulated signal transduction and abolished agonist-induced phosphorylation. Co-transfection studies revealed that the phosphorylation of these mutants can be rescued by overexpression of G protein-coupled receptor kinase 2, but this increased phosphorylation only rescues the internalization of rFSHR-D389N. The internalization of both mutants could be rescued by overexpression of arrestin-3, however. Taken together, these results argue that the agonist-induced activation and phosphorylation of the rFSHR are not essential for internalization. while the interaction of the rFSHR with a nonvisual arrestin is essential for internalization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24346-54
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9733722-Amino Acid Substitution, pubmed-meshheading:9733722-Animals, pubmed-meshheading:9733722-Arrestins, pubmed-meshheading:9733722-Base Sequence, pubmed-meshheading:9733722-Cattle, pubmed-meshheading:9733722-Cell Line, pubmed-meshheading:9733722-Cloning, Molecular, pubmed-meshheading:9733722-Cyclic AMP, pubmed-meshheading:9733722-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:9733722-Follicle Stimulating Hormone, pubmed-meshheading:9733722-G-Protein-Coupled Receptor Kinase 2, pubmed-meshheading:9733722-Humans, pubmed-meshheading:9733722-Mutagenesis, Site-Directed, pubmed-meshheading:9733722-Phosphorylation, pubmed-meshheading:9733722-Point Mutation, pubmed-meshheading:9733722-Polymerase Chain Reaction, pubmed-meshheading:9733722-Protein Structure, Secondary, pubmed-meshheading:9733722-Rats, pubmed-meshheading:9733722-Receptors, FSH, pubmed-meshheading:9733722-Recombinant Proteins, pubmed-meshheading:9733722-Signal Transduction, pubmed-meshheading:9733722-Tetradecanoylphorbol Acetate, pubmed-meshheading:9733722-Transfection, pubmed-meshheading:9733722-beta-Adrenergic Receptor Kinases
pubmed:year
1998
pubmed:articleTitle
Signaling and phosphorylation-impaired mutants of the rat follitropin receptor reveal an activation- and phosphorylation-independent but arrestin-dependent pathway for internalization.
pubmed:affiliation
Department of Pharmacology, The University of Iowa College of Medicine Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't