Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide
receptor signaling by protein kinase C and beta-arrestins
M. Castro, F. Dicker, J. Vilardaga, C. Krasel, M. Bernhardt, and M. Lohse. Endocrinology, 143 (10):
3854-65(October 2002)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..
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.
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.
%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
}