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Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling

BACKGROUND: G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bin...

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Autores principales: Liu, Andrew MF, Lo, Rico KH, Guo, Emily X, Ho, Maurice KC, Ye, Richard D, Wong, Yung H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098143/
https://www.ncbi.nlm.nih.gov/pubmed/21486497
http://dx.doi.org/10.1186/1472-6807-11-17
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author Liu, Andrew MF
Lo, Rico KH
Guo, Emily X
Ho, Maurice KC
Ye, Richard D
Wong, Yung H
author_facet Liu, Andrew MF
Lo, Rico KH
Guo, Emily X
Ho, Maurice KC
Ye, Richard D
Wong, Yung H
author_sort Liu, Andrew MF
collection PubMed
description BACKGROUND: G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bind a multitude of effectors and regulatory proteins. Yet it remains unclear if the different proteins utilize distinct or common structural motifs on the Gα subunit for binding. Using Gα(16 )as a model, we asked if its recently discovered adaptor protein tetratricopeptide repeat 1 (TPR1) binds to the same region as its canonical effector, phospholipase Cβ (PLCβ). RESULTS: We have examined the specificity of Gα(16)/TPR1 association by testing a series of chimeras between Gα(16 )and Gα(z). TPR1 co-immunoprecipitated with Gα(16 )and more tightly with its constitutively active Gα(16)QL, but not Gα(z). Progressive replacement of Gα(16 )sequence with the corresponding residues of Gα(z )eventually identified a stretch of six amino acids in the β3 region of Gα(16 )which are responsible for TPR1 interaction and the subsequent Ras activation. Insertion of these six residues into Gα(z )allowed productive TPR1-interaction. Since the β3 region only minimally contributes to interact with PLCβ, several chimeras exhibited differential abilities to stimulate PLCβ and Ras. The ability of the chimeras to activate downstream transcription factors such as signal transducer and activator of transcription 3 and nuclear factor κB appeared to be associated with PLCβ signaling. CONCLUSIONS: Our results suggest that Gα(16 )can signal through TPR1/Ras and PLCβ simultaneously and independently. The β3 region of Gα(16 )is essential for interaction with TPR1 and the subsequent activation of Ras, but has relatively minor influence on the PLCβ interaction. Gα(16 )may utilize different structural domains to bind TPR1 and PLCβ.
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spelling pubmed-30981432011-05-20 Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling Liu, Andrew MF Lo, Rico KH Guo, Emily X Ho, Maurice KC Ye, Richard D Wong, Yung H BMC Struct Biol Research Article BACKGROUND: G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bind a multitude of effectors and regulatory proteins. Yet it remains unclear if the different proteins utilize distinct or common structural motifs on the Gα subunit for binding. Using Gα(16 )as a model, we asked if its recently discovered adaptor protein tetratricopeptide repeat 1 (TPR1) binds to the same region as its canonical effector, phospholipase Cβ (PLCβ). RESULTS: We have examined the specificity of Gα(16)/TPR1 association by testing a series of chimeras between Gα(16 )and Gα(z). TPR1 co-immunoprecipitated with Gα(16 )and more tightly with its constitutively active Gα(16)QL, but not Gα(z). Progressive replacement of Gα(16 )sequence with the corresponding residues of Gα(z )eventually identified a stretch of six amino acids in the β3 region of Gα(16 )which are responsible for TPR1 interaction and the subsequent Ras activation. Insertion of these six residues into Gα(z )allowed productive TPR1-interaction. Since the β3 region only minimally contributes to interact with PLCβ, several chimeras exhibited differential abilities to stimulate PLCβ and Ras. The ability of the chimeras to activate downstream transcription factors such as signal transducer and activator of transcription 3 and nuclear factor κB appeared to be associated with PLCβ signaling. CONCLUSIONS: Our results suggest that Gα(16 )can signal through TPR1/Ras and PLCβ simultaneously and independently. The β3 region of Gα(16 )is essential for interaction with TPR1 and the subsequent activation of Ras, but has relatively minor influence on the PLCβ interaction. Gα(16 )may utilize different structural domains to bind TPR1 and PLCβ. BioMed Central 2011-04-13 /pmc/articles/PMC3098143/ /pubmed/21486497 http://dx.doi.org/10.1186/1472-6807-11-17 Text en Copyright ©2011 Liu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Andrew MF
Lo, Rico KH
Guo, Emily X
Ho, Maurice KC
Ye, Richard D
Wong, Yung H
Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title_full Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title_fullStr Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title_full_unstemmed Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title_short Gα(16 )interacts with tetratricopeptide repeat 1 (TPR1) through its β3 region to activate Ras independently of phospholipase Cβ signaling
title_sort gα(16 )interacts with tetratricopeptide repeat 1 (tpr1) through its β3 region to activate ras independently of phospholipase cβ signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098143/
https://www.ncbi.nlm.nih.gov/pubmed/21486497
http://dx.doi.org/10.1186/1472-6807-11-17
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