Linked Life Data

7592895

Source:http://linkedlifedata.com/resource/pubmed/id/7592895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
1995-12-21
pubmed:abstractText
We have recently shown that addition of follitropin (FSH) or a phorbol ester (phorbol 12-myristate 13-acetate (PMA)) to cells expressing the recombinant follitropin receptor (FSHR) results in both phosphorylation and uncoupling of the FSHR from adenylyl cyclase. In the light of findings reported with other G protein-coupled receptors we have proposed that phosphorylation of the FSHR mediates the uncoupling from adenylyl cyclase. The experiments described herein represent the first attempt to determine the location of the amino acid residues that become phosphorylated in FSHR and to test the hypothesis that phosphorylation is responsible for uncoupling of FSHR from adenylyl cyclase. As a first step in identifying which residues may be phosphorylated in response to hFSH and PMA, we constructed a mutant of the FSHR cDNA in which the C-terminal cytoplasmic tail was truncated at residue 635 (FSHR-t635), thus removing all but one of the potential phosphorylation sites present in the C-terminal tail. Cells expressing FSHR-t635 bind hFSH with the appropriate affinity and respond with increases in cAMP and inositol phosphate accumulation. The maximal cAMP and inositol phosphate responses of cells expressing FSHR-t635 are higher than those of cells expressing the wild type FSHR, but the concentration of hFSH required to elecit these responses is similar in both cell lines. Immunoprecipitation of FSHR-t635 shows that the truncated receptor is still effectively phosphorylated in response to hFSH or PMA. Phosphoamino acid analysis reveals that, like the wild-type FSHR, FSHR-t635 phosphorylation occurs on serine and threonine residues. Peptide mapping suggests that the phosphorylated residues in the FSHR and FSHR-t635 are located within the same areas of the intracellular regions of the receptors. In addition to stimulating phosphorylation of FSHR-t635, hFSH and PMA also effectively uncouple the truncated receptor from adenylyl cyclase. Taken together, these data show that hFSH and PMA can both phosphorylate and uncouple a FSH receptor species with a cytoplasmic tail truncated at residue 635.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26683-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7592895-Adenylate Cyclase, pubmed-meshheading:7592895-Amino Acid Sequence, pubmed-meshheading:7592895-Animals, pubmed-meshheading:7592895-Cell Line, pubmed-meshheading:7592895-Cloning, Molecular, pubmed-meshheading:7592895-Follicle Stimulating Hormone, pubmed-meshheading:7592895-Humans, pubmed-meshheading:7592895-Molecular Sequence Data, pubmed-meshheading:7592895-Phosphates, pubmed-meshheading:7592895-Phosphorylation, pubmed-meshheading:7592895-Polymerase Chain Reaction, pubmed-meshheading:7592895-Protein Structure, Secondary, pubmed-meshheading:7592895-Rats, pubmed-meshheading:7592895-Receptors, FSH, pubmed-meshheading:7592895-Recombinant Proteins, pubmed-meshheading:7592895-Structure-Activity Relationship, pubmed-meshheading:7592895-Tetradecanoylphorbol Acetate, pubmed-meshheading:7592895-Transfection
pubmed:year
1995
pubmed:articleTitle
Truncation of the C-terminal tail of the follitropin receptor does not impair the agonist- or phorbol ester-induced receptor phosphorylation and uncoupling.
pubmed:affiliation
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242-1109, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't