Myocyte Stress Protein 1 (MS1) is a muscle-specific, stress-responsive, regulator of gene expression. It was originally identified in embryonic mouse heart which showed increased expression in a rat model of left ventricular hypertrophy. To determine if MS1 was responsive to other stresses relevant to cardiac myocyte function, we tested if it could be induced by the metabolic stresses associated with ischaemia/reperfusion injury in cardiac myocytes. We found that metabolic stress increased MS1 expression, both at the mRNA and protein level, concurrent with activation of the c-Jun N-terminal Kinase (JNK) signalling pathway. MS1 induction by metabolic stress was blocked by both the transcription inhibitor actinomycin D and a JNK inhibitor, suggesting that activation of the JNK pathway during metabolic stress in cardiac myocytes leads to transcriptional induction of MS1. MS1 was also found to be an efficient JNK substrate in vitro, with a major JNK phosphorylation site identified at Thr-62. In addition, MS1 was found to co-precipitate with JNK, and inspection of the amino acid sequence upstream of the phosphorylation site, at Thr-62, revealed a putative Mitogen-Activated Protein Kinase (MAPK) binding site. Taken together, these data identify MS1 as a likely transcriptional and post-translational target for the JNK pathway in cardiac myocytes subjected to metabolic stress.
Keyphrases
- ms ms
- signaling pathway
- left ventricular
- mass spectrometry
- cell death
- gene expression
- multiple sclerosis
- induced apoptosis
- amino acid
- transcription factor
- binding protein
- poor prognosis
- heart failure
- dna methylation
- squamous cell carcinoma
- tyrosine kinase
- liquid chromatography
- cell proliferation
- protein protein
- coronary artery disease
- aortic valve
- heat stress
- hypertrophic cardiomyopathy
- cardiac resynchronization therapy
- percutaneous coronary intervention
- single cell
- aortic stenosis
- ejection fraction
- transcatheter aortic valve replacement
- big data
- heat shock