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Key Event Title
Overexpression of rasl11b
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Key Event Components
Key Event Overview
AOPs Including This Key Event
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|Inhibition of Fyna leading to increased mortality||KeyEvent||Vid Modic (send email)||Open for citation & comment|
Key Event Description
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
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
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).
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