Linked Life Data

12239097

Source:http://linkedlifedata.com/resource/pubmed/id/12239097

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-9-19
pubmed:abstractText
We examined here the role of second messenger-dependent kinases and beta-arrestins in short-term regulation of the PTH receptor (PTHR) signaling. The inhibition of protein kinase C (PKC) in COS-7 cells transiently expressing PTHR, led to an approximately 2-fold increase in PTH-stimulated inositol phosphate (IP) and cAMP production. The inhibition of protein kinase A increased cAMP production 1.5-fold without affecting IP signaling. The effects of PKC inhibition on PTHR-mediated G(q) signaling were strongly decreased for a carboxy-terminally truncated PTHR (T480) that is phosphorylation deficient. PKC inhibition was associated with a decrease in agonist-stimulated PTHR phosphorylation and internalization without blocking PTH-dependent mobilization of beta-arrestin2 to the plasma membrane. Overexpression of beta-arrestins strongly decreased the PTHR-mediated IP signal, whereas cAMP production was impaired to a much lower extent. The regulation of PTH-stimulated signals by beta-arrestins was impaired for the truncated T480 receptor. Our data reveal mechanisms at, and distal to, the receptor regulating PTHR-mediated signaling pathways by second messenger-dependent kinases. We conclude that regulation of PTHR-mediated signaling by PKC and beta-arrestins are separable phenomena that both involve the carboxy terminus of the receptor. A major role for PKC and beta-arrestins in preferential regulation of PTHR-mediated G(q) signaling by independent mechanisms at the receptor level was established.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3854-65
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins.
pubmed:affiliation
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't