ArticleMolecular biology of the cell2016
Regulatory roles of conserved phosphorylation sites in the activation T-loop of the MAP kinase ERK1.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
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- Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker.Nature communications · 2021Article
- A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.International microbiology : the official journal of the Spanish Society for Microbiology · 2021Review
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- Differential Role of Threonine and Tyrosine Phosphorylation in the Activation and Activity of the Yeast MAPK Slt2.International journal of molecular sciences · 2021Article
- Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
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- Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy.Cardiology journal · 2021Review
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention.Nature communications · 2020Article
- Nitration-induced ubiquitination and degradation control quality of ERK1.The Biochemical journal · 2019Article
- Metformin Promotes Neuronal Differentiation via Crosstalk between Cdk5 and Sox6 in Neuroblastoma Cells.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Comprehensive genomic analysis of the CNGC gene family in Brassica oleracea: novel insights into synteny, structures, and transcript profiles.BMC genomics · 2017Article
- Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop.Scientific reports · 2017Article
- Tyr(less) kinase signaling during mitosis.Cell cycle (Georgetown, Tex.) · 2017Article
- Classifying kinase conformations using a machine learning approach.BMC bioinformatics · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The catalytic domains of most eukaryotic protein kinases are highly conserved in their primary structures. Their phosphorylation within the well-known activation T-loop, a variable region between protein kinase catalytic subdomains VII and VIII, is a common mechanism for stimulation of their phosphotransferase activities. Extracellular signal-regulated kinase 1 (ERK1), a member of the extensively studied mitogen-activated protein kinase (MAPK) family, serves as a paradigm for regulation of protein kinases in signaling modules. In addition to the well-documented T202 and Y204 stimulatory phosphorylation sites in the activation T-loop of ERK1 and its closest relative, ERK2, three additional flanking phosphosites have been confirmed (T198, T207, and Y210 from ERK1) by high-throughput mass spectrometry. In vitro kinase assays revealed the functional importance of T207 and Y210, but not T198, in negatively regulating ERK1 catalytic activity. The Y210 site could be important for proper conformational arrangement of the active site, and a Y210F mutant could not be recognized by MEK1 for phosphorylation of T202 and Y204 in vitro. Autophosphorylation of T207 reduces the catalytic activity and stability of activated ERK1. We propose that after the activation of ERK1 by MEK1, subsequent slower phosphorylation of the flanking sites results in inhibition of the kinase. Because the T207 and Y210 phosphosites of ERK1 are highly conserved within the eukaryotic protein kinase family, hyperphosphorylation within the kinase activation T-loop may serve as a general mechanism for protein kinase down-regulation after initial activation by their upstream kinases.
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