ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth
Abstract
Simple Summary
Abstract
1. Introduction
2. The ERK1/2 Signaling Module
3. Sensing of Extracellular Stimuli That Modulate ERK1/2 Activity in Cardiomyocytes
3.1. Integrins
3.2. G-Protein-Coupled Receptors
3.3. Receptor Tyrosine Kinases
4. Integration of ERK1/2 Signaling for Cardiomyocyte Homeostasis and Stress Responses
4.1. Modulation of ERK Kinase Cascade in Cardiomyocyte
4.2. Scaffolds in Regulation of ERK Signaling in the Heart
4.3. Impact of Cardiac ERK Signal Termination by Phosphatases
4.4. ERK in Heart Failure Onset and Progression
4.5. Cardiac Ramifications of Therapeutic ERK Inhibition
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Localization | Gene Name | Protein Name | Role/Function | References |
---|---|---|---|---|
Plasma Membrane | CAPN2 | Calpain-2 catalytic subunit | Plays a role in epidermal growth factor (EGF)-mediated cell adhesion and motility. | [27,28,29] |
NOXA1 | NADPH oxidase activator 1 | Activates NADPH oxidase NOX1 to produce reactive oxygen species (ROS) that play a role in host defense, hormone biosynthesis, and sensing. | [29,30] | |
Cytoskeleton | AKAP12 | A-kinase anchor protein 12 | Anchors protein kinases A (PKA) and C (PKC) and plays a role in cell cycle regulation. | [29,31,32,33,34] |
AMPH | Amphiphysin | Plays a role in endoyctosis. | [29,35,36,37] | |
MAP1B | Microtubule-associated protein 1B | Plays a role in neurite extension, where phosphorylation may induce microtubule association. | [29,32,33,34] | |
TNKS1BP1 | 182 kDa tankyrase-1-binding protein | Functions in regulating the actin cytoskeleton. | [29,33,34,38] | |
Cytosol | DCP1A | mRNA-decapping enzyme 1A | Modulates gene expression through interaction with decapping enzyme Dcp2. | [29,33,39] |
RPS3 | 40S ribosomal protein S3 | Functions as a member of the ribosomal small subunit; plays a role in DNA repair. | [29,32,33,34,40] | |
RPS6KA1 | Ribosomal protein S6 kinase alpha-1 (RSK1) | Acts downstream of ERK found in both the cytosol and nucleus. | [29,41] | |
RPS6KA3 | Ribosomal protein S6 kinase alpha-3 (RSK2) | Acts downstream of ERK found in both the cytosol and nucleus. | [29,41] | |
RPS6KA2 | Ribosomal protein S6 kinase alpha-2 (RSK3) | Acts downstream of ERK found in both the cytosol and nucleus. | [29,41] | |
SPHK1 | Sphingosine kinase 1 | Activates proteins tied to proliferation and repression of apoptosis following activation through phosphorylation. | [29,42] | |
STAT1 | Signal transducer and activator of transcription 1-alpha/beta | Transduces interferon-, growth factor-, and cytokine-mediated signals. | [29,33,43,44] | |
STIM1 | Stromal interaction molecule 1 | Upon intracellular Ca2+ depletion, translocates from the ER membrane to near the plasma membrane to activate store-operated calcium channels (SOCs). | [29,45] | |
TP53 | Cellular tumor antigen p53 | Functions as a cell cycle regulator and tumor suppressor. | [29,46] | |
Nucleus | AHNAK | Neuroblast differentiation-associated protein AHNAK | May be required for neuronal cell differentiation; has been observed to disrupt PKC-PP2A complex to upregulate ERK signaling in NIH3T3 fibroblasts. | [29,32,34,47,48,49,50] |
ATF2 | Cyclic AMP-dependent transcription factor ATF-2 | Upon phosphorylation, upregulates genes tied to DNA damage response and cell growth. | [29,37,51] | |
CEBPB | CCAAT/enhancer-binding protein beta | Phosphorylation of the CCAAT/enhancer-binding protein-b (C/EBPb) by ERK2 (not ERK1) enhances its interaction with SRF and its transactivation activity. | [29,52] | |
ELK1 | ETS domain-containing protein Elk-1 | Primarily functions to transcribe c-Fos, which plays a role in cell proliferation and differentiation; phosphorylation enhances activity. | [29,37,53] | |
EP300 | Histone acetyltransferase p300 | Regulates transcription via chromatin remodeling. | [29,54] | |
ETS1 | Protein C-ets-1 | Regulates immune cell function. | [29,55] | |
FAM195B | Mapk-regulated corepressor-interacting protein 1 | Regulates co-repressor CtBP to mediate gene silencing during the epithelial-mesenchymal transition. | [29,34,56] | |
FOXO3 | Forkhead box protein O3 | Regulates cellular processes, such as apoptosis and autophagy, where nuclear translocation occurs in response to stress. | [29,57] | |
HNRNPH1 | Heterogeneous nuclear ribonucleoprotein H | Mediates pre-mRNA splicing. | [58] | |
JUN | Transcription factor AP-1 (c-Jun) | Plays an integral role in cell cycle progression. | [29,32,37] | |
MCL1 | Induced myeloid leukemia cell differentiation protein Mcl-1 | Plays a role in regulating apoptosis. | [29,59] | |
NDF1 | Neurogenic differentiation factor 1 | Regulates differentiation of neuronal and endocrine cells. | [29,37,60] | |
NR5A1 | Steroidogenic factor 1 | Plays a role in the development of the primary steroidogenic tissues in both sexes. | [29,61] | |
NUP153 | Nuclear pore complex protein Nup153 | Functions trafficking across the nuclear envelope. | [29,32,33,34,62,63] | |
PRRC2A | Protein PRRC2A (BAT2) | Functions in oligodendrocyte specification; plays a role in pre-mRNA splicing. | [29,33,34,50,64] | |
RPS6KA5 | Ribosomal protein S6 kinase alpha-5 (MSK1) | Upon activations, functions to phosphorylate CREB1 and ATF1 in response to mitogenic or stress signaling. | [29,41] | |
SMAD4 | Mothers against decapentaplegic homolog 4 | Balances atrophy and hypertrophy, where nuclear translocation occurs R-SMAD; Component of nuclear SMAD2/SMAD3-SMAD4 complex. | [29,37,65] | |
TAL1 | T-cell acute lymphocytic leukemia protein 1 | Serves as a positive regulator of erythroid differentiation. | [29,37,66] | |
TPR | Nucleoprotein TPR | Functions trafficking across the nuclear envelope; plays an integral role in cell division. | [29,32,34,50,67] | |
XRN2 | 5’-3’ exoribonuclease 2 | Functions in RNA degradation. | [29,32,34,68] |
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Gilbert, C.J.; Longenecker, J.Z.; Accornero, F. ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth. Biology 2021, 10, 346. https://doi.org/10.3390/biology10040346
Gilbert CJ, Longenecker JZ, Accornero F. ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth. Biology. 2021; 10(4):346. https://doi.org/10.3390/biology10040346
Chicago/Turabian StyleGilbert, Christopher J., Jacob Z. Longenecker, and Federica Accornero. 2021. "ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth" Biology 10, no. 4: 346. https://doi.org/10.3390/biology10040346
APA StyleGilbert, C. J., Longenecker, J. Z., & Accornero, F. (2021). ERK1/2: An Integrator of Signals That Alters Cardiac Homeostasis and Growth. Biology, 10(4), 346. https://doi.org/10.3390/biology10040346