Dataset Information

Mitochondrial CaMKII phosphoproteome.

ABSTRACT: Mice overexpressing CaMKII in myocardial mitochondria have dilated cardiomyopathy that appears to be exclusively driven by metabolic defects that lead to reduced ATP production. Phosphoproteomics study of mitochondrial proteins supports the metabolomics data.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Eleonora Corradini

LAB HEAD: Albert J.R. Heck

PROVIDER: PXD004631 | Pride | 2020-07-31

REPOSITORIES: Pride

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Publications

Mitochondrial CaMKII causes adverse metabolic reprogramming and dilated cardiomyopathy.

Luczak Elizabeth D ED Wu Yuejin Y Granger Jonathan M JM Joiner Mei-Ling A MA Wilson Nicholas R NR Gupta Ashish A Umapathi Priya P Murphy Kevin R KR Reyes Gaido Oscar E OE Sabet Amin A Corradini Eleonora E Tseng Wen-Wei WW Wang Yibin Y Heck Albert J R AJR Wei An-Chi AC Weiss Robert G RG Anderson Mark E ME

Nature communications 20200904 1

Despite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. Here, we report increased mitochondrial calmodulin kinase II (CaMKII) activation and left ventricular dilation in mice one week after myocardial infarction (MI) surgery. By contrast, mice with genetic mitochondrial CaMKII inhibition are protected from left ventricular dilation ...[more]

PMID: 32887881

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Project description:Albeit much less abundant than Ser/Thr phosphorylation (pSer/pThr), Tyr phosphorylation (pTyr) is considered a hallmark in cellular signal transduction. However, its analysis remains a challenge. The conventional immunopurification (IP) approach using antibodies pan-specific to pTyr sites is known to have low sensitivity, poor reproducibility and high cost. SH2 domain-derived pTyr-superbinder is a good replacement of pTyr antibody for the specific enrichment of pTyr peptides for phosphoproteomics analysis. In this study, we aim to optimize the approach using SH2 superbinder for tyrosine phosphoproteome analysis. The present work covalently immobilized SH2 superbinders to agrose beads, designed and evaluated four different SH2 superbinder based experimental workflows for phosphotyrosine analysis. After made a head to head comparison of them, we observed that the combined strategy employing Ti4+-IMAC and covalently immobilized SH2 superbinder enrichment in sequence generated the largest pTyr peptide dataset (3519) with the best selectivity (90%). Next the optimal method was applied for pTyr profiling from normal mouse tissues, and resulted in the identification of 197 pTyr sites (of which 73 were novel) from 5 mg protein digests, which validated its high sensitivity. An comparison with antibody 4G10 by isolating pTyr peptides from 5 mg unstimulated Jurkat cell digests were made, our optimal strategy identified 343 while the antibody 4G10 based method identified 242 pTyr sites, respectively, further confirmed the robustness of the method. Finally, the optimal strategy was applied for quantitative pTyr phosphorylation analysis of EGF stimulated/unstimulated HeLa cells, 261 pTyr sites were successfully quantified from 5 mg stable-isotope dimethyl labling protein digests. In general, the combination of Ti4+-IMAC and SH2 superbinder enrichment in sequence generated a facial and robust strategy for qualitative and quantitative analysis of pTyr proteome.

Dataset Information

Mitochondrial CaMKII phosphoproteome.

Publications

Mitochondrial CaMKII causes adverse metabolic reprogramming and dilated cardiomyopathy.

Similar Datasets

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