Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated
by Gbetagamma exchange
U. Quitterer, and M. Lohse. Proc Natl Acad Sci U S A, 96 (19):
10626-31(September 1999)Quitterer, U Lohse, M J United states Proceedings of the National
Academy of Sciences of the United States of America Proc Natl Acad
Sci U S A. 1999 Sep 14;96(19):10626-31..
Abstract
Activation of Galpha(i)-coupled receptors often causes enhancement
of the inositol phosphate signal triggered by Galpha(q)-coupled receptors.
To investigate the mechanism of this synergistic receptor crosstalk,
we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic
receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring
P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed
in COS cells increased the potency and the efficacy of inositol phosphate
production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2)
resulted in a similar increase in potency and efficacy of bradykinin
or UTP. In contrast, these stimuli did not affect the potency of
direct activators of Galpha(q); a truncated Gbeta(3) mutant had no
effect on the receptor-generated signals whereas signals generated
at the G-protein level were still enhanced. This suggests that the
Gbetagamma-mediated signal enhancement occurs at the receptor level.
Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were
equally effective in enhancing the signals of the B(2) and a UTP-preferring
P2Y receptor, indicating a very broad specificity of this synergism.
The enhancement of the bradykinin signal by (i) Galpha(i)-activating
receptor ligands or (ii) cotransfection of Gbetagamma was suppressed
when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein.
Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins
as determined by GTPgammaS-induced decrease in high affinity agonist
binding and by B(2) receptor-enhanced (35)SGTPgammaS binding. These
findings support the concept that Gbetagamma exchange between Galpha(i)-
and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.
Quitterer, U Lohse, M J United states Proceedings of the National
Academy of Sciences of the United States of America Proc Natl Acad
Sci U S A. 1999 Sep 14;96(19):10626-31.
%0 Journal Article
%1 Quitterer1999
%A Quitterer, U.
%A Lohse, M. J.
%D 1999
%J Proc Natl Acad Sci U S A
%K Animals B2 Biological Bradykinin Bradykinin/*metabolism C COS Calcium/metabolism Cross-Talk/*physiology Dose-Response Drug Factors Fusion GTP-Binding Immunoblotting Inositol Models, Mutagenesis Phosphates/metabolism Phospholipases/metabolism Proteins/metabolism Receptor Recombinant Relationship, Signal Time Transduction Transfection Triphosphate/metabolism Type Uridine beta-2/metabolism Cell Adrenergic
%N 19
%P 10626-31
%T Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated
by Gbetagamma exchange
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10485876
%V 96
%X Activation of Galpha(i)-coupled receptors often causes enhancement
of the inositol phosphate signal triggered by Galpha(q)-coupled receptors.
To investigate the mechanism of this synergistic receptor crosstalk,
we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic
receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring
P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed
in COS cells increased the potency and the efficacy of inositol phosphate
production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2)
resulted in a similar increase in potency and efficacy of bradykinin
or UTP. In contrast, these stimuli did not affect the potency of
direct activators of Galpha(q); a truncated Gbeta(3) mutant had no
effect on the receptor-generated signals whereas signals generated
at the G-protein level were still enhanced. This suggests that the
Gbetagamma-mediated signal enhancement occurs at the receptor level.
Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were
equally effective in enhancing the signals of the B(2) and a UTP-preferring
P2Y receptor, indicating a very broad specificity of this synergism.
The enhancement of the bradykinin signal by (i) Galpha(i)-activating
receptor ligands or (ii) cotransfection of Gbetagamma was suppressed
when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein.
Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins
as determined by GTPgammaS-induced decrease in high affinity agonist
binding and by B(2) receptor-enhanced (35)SGTPgammaS binding. These
findings support the concept that Gbetagamma exchange between Galpha(i)-
and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.
@article{Quitterer1999,
abstract = {Activation of Galpha(i)-coupled receptors often causes enhancement
of the inositol phosphate signal triggered by Galpha(q)-coupled receptors.
To investigate the mechanism of this synergistic receptor crosstalk,
we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic
receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring
P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed
in COS cells increased the potency and the efficacy of inositol phosphate
production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2)
resulted in a similar increase in potency and efficacy of bradykinin
or UTP. In contrast, these stimuli did not affect the potency of
direct activators of Galpha(q); a truncated Gbeta(3) mutant had no
effect on the receptor-generated signals whereas signals generated
at the G-protein level were still enhanced. This suggests that the
Gbetagamma-mediated signal enhancement occurs at the receptor level.
Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were
equally effective in enhancing the signals of the B(2) and a UTP-preferring
P2Y receptor, indicating a very broad specificity of this synergism.
The enhancement of the bradykinin signal by (i) Galpha(i)-activating
receptor ligands or (ii) cotransfection of Gbetagamma was suppressed
when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein.
Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins
as determined by GTPgammaS-induced decrease in high affinity agonist
binding and by B(2) receptor-enhanced [(35)S]GTPgammaS binding. These
findings support the concept that Gbetagamma exchange between Galpha(i)-
and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Quitterer, U. and Lohse, M. J.},
biburl = {https://www.bibsonomy.org/bibtex/25e1cb306b6619de6f426960ca1140842/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {4d830b578416e23820a79bf400ef9a28},
intrahash = {5e1cb306b6619de6f426960ca1140842},
issn = {0027-8424 (Print) 0027-8424 (Linking)},
journal = {Proc Natl Acad Sci U S A},
keywords = {Animals B2 Biological Bradykinin Bradykinin/*metabolism C COS Calcium/metabolism Cross-Talk/*physiology Dose-Response Drug Factors Fusion GTP-Binding Immunoblotting Inositol Models, Mutagenesis Phosphates/metabolism Phospholipases/metabolism Proteins/metabolism Receptor Recombinant Relationship, Signal Time Transduction Transfection Triphosphate/metabolism Type Uridine beta-2/metabolism Cell Adrenergic},
month = {Sep 14},
note = {Quitterer, U Lohse, M J United states Proceedings of the National
Academy of Sciences of the United States of America Proc Natl Acad
Sci U S A. 1999 Sep 14;96(19):10626-31.},
number = 19,
pages = {10626-31},
shorttitle = {Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated
by Gbetagamma exchange},
timestamp = {2010-12-14T18:22:42.000+0100},
title = {Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated
by Gbetagamma exchange},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10485876},
volume = 96,
year = 1999
}