Natriuretic peptide receptor-C releases and activates guanine nucleotide-exchange factor H1 in a ligand-dependent manner

Autor: Yuki Shimizu, Akihiko Tsuji, Shogo Abe, Maki Shimada, Mika Nishida, Kenji Miyamoto, Keizo Yuasa
Rok vydání: 2021
Předmět:
0301 basic medicine
animal structures
medicine.drug_class
Gi alpha subunit
Biophysics
Muscle Proteins
Ligands
environment and public health
Biochemistry
Adenylyl cyclase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Serine
Natriuretic peptide
medicine
Animals
Humans
Phosphorylation
Receptor
Molecular Biology
Chemistry
Kinase
Binding protein
fungi
Cell Biology
Cell biology
enzymes and coenzymes (carbohydrates)
HEK293 Cells
030104 developmental biology
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
030220 oncology & carcinogenesis
biological phenomena
cell phenomena
and immunity
rhoA GTP-Binding Protein
Receptors
Atrial Natriuretic Factor
Rho Guanine Nucleotide Exchange Factors
Intracellular
HeLa Cells
Protein Binding
Signal Transduction
Transcription Factors
Zdroj: Biochemical and Biophysical Research Communications. 552:9-16
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2021.03.028
Popis: Although natriuretic peptide receptor-C (NPR-C) is involved in the clearance of natriuretic peptides from plasma, it also possesses other physiological functions, such as inhibition of adenylyl cyclase activity through Gαi. However, the physiological roles and intracellular signaling pathways of NPR-C have yet been not fully elucidated. In this study, we identified a RhoA-specific guanine nucleotide-exchange factor, GEF-H1, as a novel binding protein of NPR-C. We demonstrated that endogenous NPR-C interacted with GEF-H1 in HeLa cells, and that the interaction between NPR-C and GEF-H1 was dependent on a 37-amino acid cytoplasmic region of NPR-C. In contrast, another natriuretic peptide receptor, NPR-A, which includes the kinase homology and guanylyl cyclase domains in the intracellular region, did not interact with GEF-H1. We also revealed that the ligands of NPR-C (i.e., ANP, CNP, and osteocrin) caused dissociation of GEF-H1 from NPR-C. Furthermore, osteocrin treatment induced phosphorylation of GEF-H1 at Ser-886, enhanced the interaction of GEF-H1 with 14-3-3, and increased the amount of activated GEF-H1. These findings strongly supported that NPR-C may be involved in diverse physiological roles by regulating GEF-H1 signaling.
Databáze: OpenAIRE
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