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Event: 2146

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Activation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase 1/2

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Activation of MEK, ERK1/2
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
astrocyte

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
brain

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
kinase activity astrocyte increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
MEK-ERK1/2 activation leading to deficits in learning and cognition MolecularInitiatingEvent Travis Karschnik (send email) Under development: Not open for comment. Do not cite
MEK-ERK1/2 activation leading to deficits in learning and cognition via ROS MolecularInitiatingEvent Travis Karschnik (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Rattus norvegicus Rattus norvegicus Moderate NCBI
Mus musculus Mus musculus Moderate NCBI
Homo sapiens Homo sapiens Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Mixed Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

ERK1 and ERK2 are proteins of 43 and 41 kDa that are nearly 85% identical overall, with much greater identity in the core regions involved in binding substrates (Boulton et al., 1990; 1991). The two phosphoacceptor sites, tyrosine and threonine, which are phosphorylated to activate the kinases, are separated by a glutamate residue in both ERK1 and ERK2 to give the motif TEY in the activation loop (Payne et al., 1991). Both are ubiquitously expressed, although their relative abundance in tissues is variable. For example, in many immune cells ERK2 is the predominant species, while in several cells of neuroendocrine origin they may be equally expressed (Gray Pearson and others 2001). They are stimulated to some extent by a vast number of ligands and cellular perturbations, with some cell type specificity (Lewis et al., 1998). In fibroblasts (the cell type in which the generalizations about their behavior and functions have been developed) they are activated by serum, growth factors, cytokines, certain stresses, ligands for G protein-coupled receptors (GPCRs), and transforming agents, to name a few (Gray Pearson and others 2001). They are highly expressed in postmitotic neurons and other highly differentiated cells (Boulton et al., 1991). In these cells they are often involved in adaptive responses such as long-term potentiation (English and Sweatt 1996; Atkins et al., 1998; Rossi-Arnaud et al., 1997).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Western blotting and immunoblotting.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

Atkins CM, Selcher JC, Petraitis JJ, Trzaskos JM, Sweatt JD 1998 The MAPK cascade is required for mammalian associative learning. Nat Neurosci 1 :602 –609

Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD 1991 ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65 :663 –675

Boulton TG, Yancopoulos GD, Gregory JS, Slaughter C, Moomaw C, Hsu J, Cobb MH 1990 An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science 249 :64 –67

English JD , Sweatt JD 1996 Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J Biol Chem 271 :24329 –24332

Gray Pearson and others, Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions, Endocrine Reviews, Volume 22, Issue 2, 1 April 2001, Pages 153–183, https://doi.org/10.1210/edrv.22.2.0428

Lewis TS, Shapiro PS, Ahn NG 1998 Signal transduction through MAP kinase cascades. Adv Cancer Res 74 :49 –139

Payne DM, Rossomando AJ, Martino P, Erickson AK, Her J-H, Shananowitz J, Hunt DF, Weber MJ, Sturgill TW 1991 Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J 10 :885 –892

Rossi-Arnaud C, Grant SG, Chapman PF, Lipp HP, Sturani E, Klein R 1997 A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 390 :281 –286