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Protein Kinase C ζ Interacts with a Novel Binding Region of Gαq to Act as a Functional Effector.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2016 Apr 29; Vol. 291 (18), pp. 9513-25. Date of Electronic Publication: 2016 Feb 17. - Publication Year :
- 2016
-
Abstract
- Heterotrimeric G proteins play an essential role in the initiation of G protein-coupled receptor (GPCR) signaling through specific interactions with a variety of cellular effectors. We have recently reported that GPCR activation promotes a direct interaction between Gαq and protein kinase C ζ (PKCζ), leading to the stimulation of the ERK5 pathway independent of the canonical effector PLCβ. We report herein that the activation-dependent Gαq/PKCζ complex involves the basic PB1-type II domain of PKCζ and a novel interaction module in Gαq different from the classical effector-binding site. Point mutations in this Gαq region completely abrogate ERK5 phosphorylation, indicating that Gαq/PKCζ association is required for the activation of the pathway. Indeed, PKCζ was demonstrated to directly bind ERK5 thus acting as a scaffold between Gαq and ERK5 upon GPCR activation. The inhibition of these protein complexes by G protein-coupled receptor kinase 2, a known Gαq modulator, led to a complete abrogation of ERK5 stimulation. Finally, we reveal that Gαq/PKCζ complexes link Gαq to apoptotic cell death pathways. Our data suggest that the interaction between this novel region in Gαq and the effector PKCζ is a key event in Gαq signaling.<br /> (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Animals
CHO Cells
COS Cells
Chlorocebus aethiops
Cricetinae
Cricetulus
G-Protein-Coupled Receptor Kinases genetics
G-Protein-Coupled Receptor Kinases metabolism
GTP-Binding Protein alpha Subunits, Gq-G11 genetics
HeLa Cells
Humans
Mitogen-Activated Protein Kinase 7 genetics
Mitogen-Activated Protein Kinase 7 metabolism
Phosphorylation physiology
Protein Binding
Protein Kinase C genetics
Apoptosis physiology
GTP-Binding Protein alpha Subunits, Gq-G11 metabolism
MAP Kinase Signaling System physiology
Protein Kinase C metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 291
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26887939
- Full Text :
- https://doi.org/10.1074/jbc.M115.684308