%0 Journal Article %1 Castro2002 %A Castro, M. %A Dicker, F. %A Vilardaga, J. P. %A Krasel, C. %A Bernhardt, M. %A Lohse, M. J. %D 2002 %J Endocrinology %K 1 AMP/physiology Animals Arrestins/pharmacology/*physiology C/*physiology COS Cyclic Fragments/metabolism Hormone, Hormone/chemistry/metabolism/*physiology Hormone/pharmacology Inositol Kinase Messenger Parathyroid Peptide Phosphates/physiology Phosphotransferases/physiology Protein Second Signal Systems/physiology Transduction/*physiology Type Receptor Cell %N 10 %P 3854-65 %T Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12239097 %V 143 %X 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.

@article{Castro2002, abstract = {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.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Castro, M. and Dicker, F. and Vilardaga, J. P. and Krasel, C. and Bernhardt, M. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/26cb854c593fcf4178983e00b1d067873/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {e925fd8bce2da51a1d54ed3365dd4b7b}, intrahash = {6cb854c593fcf4178983e00b1d067873}, issn = {0013-7227 (Print) 0013-7227 (Linking)}, journal = {Endocrinology}, keywords = {1 AMP/physiology Animals Arrestins/pharmacology/*physiology C/*physiology COS Cyclic Fragments/metabolism Hormone, Hormone/chemistry/metabolism/*physiology Hormone/pharmacology Inositol Kinase Messenger Parathyroid Peptide Phosphates/physiology Phosphotransferases/physiology Protein Second Signal Systems/physiology Transduction/*physiology Type Receptor Cell}, month = Oct, note = {Castro, Marian Dicker, Frank Vilardaga, Jean-Pierre Krasel, Cornelius Bernhardt, Manfred Lohse, Martin J Research Support, Non-U.S. Gov't United States Endocrinology Endocrinology. 2002 Oct;143(10):3854-65.}, number = 10, pages = {3854-65}, shorttitle = {Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins}, timestamp = {2010-12-14T18:20:38.000+0100}, title = {Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12239097}, volume = 143, year = 2002 }