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Event: 1886

Key Event Title

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

Overexpression of rasl11b

Short name

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Biological Context

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Level of Biological Organization
Molecular

Cell term

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Organ term

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

Key Event Overview

AOPs Including This Key Event

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AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Inhibition of Fyna leading to increased mortality	KeyEvent	Vid Modic (send email)	Open for citation & comment

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
zebrafish	Danio rerio	High	NCBI

Life Stages

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

Life stage	Evidence
Larvae	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

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

Rasl11b is a member of the small GTPase protein family with a high degree of similarity to RAS proteins (Stolle et al., 2007). Predicted to have GTP binding activity and GTPase activity. Involved in mesendoderm development. Predicted to localize to membrane. Is expressed in several structures, including axis; central nervous system; presumptive ectoderm; shield; and tail bud. Orthologous to human RASL11B (RAS like family 11 member B) (ZFIN Gene: Rasl11b, n.d.). The Rasl11b protein is highly conserved among vertebrates, sharing on average 94% homology with its mammalian orthologs (Pézeron et al., 2008)

Rasl11b is highly conserved in vertebrates and is atypical to most Ras-like family members in two ways. First, it is cytosolic and lacks carboxy terminal lipid modification sites which allow for membrane anchoring (Pezeron et al., 2008). Second, it has a lower GTPase activity than Ras, and is more often in its active GTP-bound state (Colicelli, 2004). Ras proteins are well known to be involved in the mitogen-activated protein kinase (MAPK) pathway, therefore, it is hypothesized that Rasl11b acts as a negative regulator of MAPK by outcompeting Ras for its effectors such as Raf, leading to decreases in RPC proliferation seen in morphant zebrafish embryos (Emerson et al., 2017).

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

Overexpression can be measured with reverse transcription polymerase chain reaction (RT-PCR). This technique is primarily used to measure the amount of specific RNA which is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR) (Wong & Medrano, 2005). Combined RT-PCR and qPCR are routinely used for analysis of gene expression.

Domain of Applicability

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

The relationships described herein have been primarily established in zebrafish models (Emerson et al., 2017). Evidence for this KE was also provided for humans (Colicelli, 2004; He et al., 2018).

References

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

Colicelli, J. (2004). Human RAS superfamily proteins and related GTPases. Science’s STKE : Signal Transduction Knowledge Environment, 2004(250). https://doi.org/10.1126/stke.2502004re13

Emerson, S. E., St. Clair, R. M., Waldron, A. L., Bruno, S. R., Duong, A., Driscoll, H. E., Ballif, B. A., McFarlane, S., & Ebert, A. M. (2017). Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish. Developmental Dynamics, 246(7), 539–549. https://doi.org/10.1002/dvdy.24512

He, H., Dai, J., Zhuo, R., Zhao, J., Wang, H., Sun, F., Zhu, Y., & Xu, D. (2018). Study on the mechanism behind lncRNA MEG3 affecting clear cell renal cell carcinoma by regulating miR-7/RASL11B signaling. Journal of Cellular Physiology, 233(12), 9503–9515. https://doi.org/10.1002/jcp.26849

Pézeron, G., Lambert, G., Dickmeis, T., Strä Hle, U., Dé, F., Rosa, R. M., & Mourrain, P. (2008). Rasl11b Knock Down in Zebrafish Suppresses One-Eyed-Pinhead Mutant Phenotype. PLoS ONE. https://doi.org/10.1371/journal.pone.0001434

Stolle, K., Schnoor, M., Fuellen, G., Spitzer, M., Cullen, P., & Lorkowski, S. (2007). Cloning, genomic organization, and tissue-specific expression of the RASL11B gene. Biochimica et Biophysica Acta - Gene Structure and Expression, 1769(7–8), 514–524. https://doi.org/10.1016/j.bbaexp.2007.05.005

Wong, M. L., & Medrano, J. F. (2005). Real-time PCR for mRNA quantitation. 39(1), 75–85. https://doi.org/10.2144/05391RV01

ZFIN Gene: rasl11b. (n.d.). Retrieved March 19, 2021, from http://zfin.org/ZDB-GENE-040426-793