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PKG-1α mediates GATA4 transcriptional activity
- Source :
- Cellular Signalling. 28:585-594
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- GATA4, a zinc-finger transcription factor, is central for cardiac development and diseases. Here we show that GATA4 transcriptional activity is mediated by cell signaling via cGMP dependent PKG-1α activity. Protein kinase G (PKG), a serine/tyrosine specific kinase is the major effector of cGMP signaling. We observed enhanced transcriptional activity elicited by co-expressed GATA4 and PKG-1α. Phosphorylation of GATA4 by PKG-1α was detected on serine 261 (S261), while the C-terminal activation domain of GATA4 associated with PKG-1α. GATA4's DNA binding activity was enhanced by PKG-1α via by both phosphorylation and physical association. More importantly, a number of human disease-linked GATA4 mutants exhibited impaired S261 phosphorylation, pointing to defective S261 phosphorylation in the elaboration of human heart diseases. We showed S261 phosphorylation was favored by PKG-1α but not by PKA, and several other kinase signaling pathways such as MAPK and PKC. Our observations demonstrate that cGMP-PKG signaling mediates transcriptional activity of GATA4 and links defective GATA4 and PKG-1α mutations to the development of human heart disease.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
endocrine system
Cell signaling
Transcription, Genetic
Biology
Phosphorylation cascade
03 medical and health sciences
0302 clinical medicine
Humans
Phosphorylation
Promoter Regions, Genetic
Cyclic GMP
Transcription factor
Cells, Cultured
reproductive and urinary physiology
Protein kinase C
Cyclic GMP-Dependent Protein Kinase Type I
Kinase
DNA
Cell Biology
respiratory system
GATA4 Transcription Factor
Cell biology
030104 developmental biology
Biochemistry
Cardiovascular Diseases
Mutation
embryonic structures
cardiovascular system
cGMP-dependent protein kinase
Atrial Natriuretic Factor
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 08986568
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Cellular Signalling
- Accession number :
- edsair.doi.dedup.....b1ea076fa62fd60527779b81eb2b8c64