Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person Activation of RAS downstream of extracellular signals allows...
| Class:Id | Summation:5672606 |
|---|---|
| _displayName | Activation of RAS downstream of extracellular signals allows... |
| _timestamp | 2023-04-28 18:12:50 |
| created | [InstanceEdit:5672605] Rothfels, Karen, 2015-02-05 |
| modified | [InstanceEdit:5674059] Rothfels, Karen, 2015-02-10 [InstanceEdit:5678716] Rothfels, Karen, 2015-02-26 [InstanceEdit:5690613] Rothfels, Karen, 2015-04-29 [InstanceEdit:6804139] Rothfels, Karen, 2015-10-08 [InstanceEdit:8933591] Rothfels, Karen, 2016-08-08 [InstanceEdit:9833517] Rothfels, Karen, 2023-04-28 |
| text | Activation of RAS downstream of extracellular signals allows RAS:GTP to recruit BRAF to the plasma membrane, disrupting the pre-existing inactivating interaction between BRAF and the 14-3-3 protein YWHAB (Marais et al, 1997; Yamamori et al, 1995; reviewed in Cseh et al, 2014). BRAF, unique of the three mammalian RAF proteins, is constitutively phosphorylated on the conserved serine residue (446 in BRAF) in the N-terminal acidic motif (NtA). Constitutive negative charge in this region is critical for BRAF to function as an activator of other RAF molecules, allowing signal amplification (Marais et al, 1997; Mason et al, 1999; Wan et al, 2004; Garnett et al, 2005; Hu et al, 2013; reviewed in Cseh et al, 2014). RAS:GTP-bound BRAF heterodimerizes with additional RAF monomers, allowing cis-autophosphorylation in the activation loop of the second RAF protein. Once activated by BRAF in this manner, the 'receiver' kinase monomer is competent to dimerize with and transactivate other monomers in turn (Weber et al, 2001; Garnett et al, 2005; Hu et al, 2013; reviewed in Cseh et al, 2014). Intruigingly, the scaffold protein KSR1 is activated by BRAF in a manner analogous to other RAF monomers and can similarly act as a RAF activator once it is itself activated (Brennan et al, 2011; Ory et al, 2003; reviewed in Raabe and Rapp, 2003; Cseh et al, 2014). Although this pathway shows PP2A-mediated dephosphorylation of RAF and transient displacement of 14-3-3 proteins as preceding RAS and plasma membrane binding of RAF proteins, the order and dependency of these events is not clear. Both membrane binding and 14-3-3 displacement also appear to be facilitated by an interaction between RAF and the cell cycle protein Prohibitin (PHB; Rajalingam et al, 2005; reviewed in Rajalingam and Rudel, 2005; Chowdhury et al, 2014). |
| (summation) | [Reaction:5672950] "Activator" RAF:YWHAB dimer binds RAS:GTP [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by Activation of RAS downstream of extracellular signals allows... (5672606)
