Monomeric and Dimeric Models of ERK2 in Conjunction with Studies on Cellular Localization, Nuclear Translocation, and In Vitro Analysis

Lee, Sunbae

doi:10.1007/s10059-012-0023-4

Cited by 5 publications

(5 citation statements)

References 106 publications

(123 reference statements)

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“…These residues are located on the back of the kinase with a group of four leucines and the sequence PE/DHD that generates a protruding structure. ERK dimerization studies have already been extensively reviewed (Lee and Bae, 2012 ; Roskoski, 2012 ). Here we will summarize our current understanding of this process with an emphasis on differences among mammalian ERK1s and ERK2s.…”

Section: Comparing Structures and Regulation Of Erk Isoformsmentioning

confidence: 99%

ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

Buscà

Pouysségur

Lenormand

2016

Front. Cell Dev. Biol.

215

171

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The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. Many pathological situations have been associated to this pathway. More than one isoform has been described at each level of the cascade. In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 specify functional differences or are in contrast functionally redundant, constitutes an ongoing debate despite the huge amount of studies performed to date. In this review we compiled data on ERK1 vs. ERK2 gene structures, protein sequences, expression levels, structural and molecular mechanisms of activation and substrate recognition. We have also attempted to perform a rigorous analysis of studies regarding the individual roles of ERK1 and ERK2 by the means of morpholinos, siRNA, and shRNA silencing as well as gene disruption or gene replacement in mice. Finally, we comment on a recent study of gene and protein evolution of ERK isoforms as a distinct approach to address the same question. Our review permits the evaluation of the relevance of published studies in the field especially when measurements of global ERK activation are taken into account. Our analysis favors the hypothesis of ERK1 and ERK2 exhibiting functional redundancy and points to the concept of the global ERK quantity, and not isoform specificity, as being the essential determinant to achieve ERK function.

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Section: Comparing Structures and Regulation Of Erk Isoformsmentioning

confidence: 99%

ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

Buscà

Pouysségur

Lenormand

2016

Front. Cell Dev. Biol.

215

171

View full text Add to dashboard Cite

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“…The dimeric model of active ERK2 (the best characterized mitogen-activated protein kinase) was proposed from the crystal structure of phosphorylated ERK2. Despite this commonly accepted view, there are contrary experimental data47. While in vitro experiments are criticized for their non-physiological conditions, most in vivo experiments fix cell samples or use homogenates prepared from hundreds of cells.…”

Section: Discussionmentioning

confidence: 99%

Genetic visualization of protein interactions harnessing liquid phase transitions

Watanabe

Seki

Fukano

et al. 2017

Sci Rep

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Protein-protein interactions (PPIs) are essential components of cellular function. Current fluorescence-based technologies to measure PPIs have limited dynamic range and quantitative reproducibility. Here, we describe a genetically-encoded PPI visualization system that harnesses the dynamics of condensed liquid-phase transitions to analyze protein interactions in living cells. The fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners triggered a rapid concatenation/oligomerization process that drove the condensation of liquid-phase droplets for real-time analysis of the interaction with unlimited dynamic range in the fluorescence signal. Proof-of-principle studies revealed novel insights on the live cell dynamics of XIAP-Smac and ERK2-dimer interactions. A photoconvertible variant allowed time-resolved optical highlighting for PPI kinetic analysis. Our system, called Fluoppi, demonstrates the unique signal amplification properties of liquid-phase condensation to detect PPIs. The findings introduce a general method for discovery of novel PPIs and modulators of established PPIs.

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“…Based on the results of their experiments, Seidel and Graves [42], proposed that this structurally defined ERK2 docking site could represent the component which explains the common mechanism by which activated ERK2 regulates apoptosis. Thus it can be proposed that activated ERK2 in C-28/I2 chondrocytes in response to rhTNF-α, rhIL-6 or rhOSM, eventually interacts with various cytoplasmic and nuclear substrates, including Ets-1, as well as promoting the interaction of p-ERK2 with other protein scaffolds and anchoring proteins which further regulates gene transcription associated with apoptosis [43]. …”

Section: Discussionmentioning

confidence: 99%