Sandbox Reserved 1777: Difference between revisions
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==MRAS== | ==MRAS== | ||
<scene name='95/952705/Mras_structure/4'>MRAS</scene> is a monomeric GTPase and is anchored in the cell membrane by a C-terminal S-Farnesyl cysteine carboxylmethyl ester <Ref name='Zhou'> Zhou, Y., Prakash, P., Liang, H., et al. Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output. Cell, 168(1-2), 239–251.e16 doi: 10.1016/j.cell.2016.11.059. [https://doi.org/10.1016/j.cell.2016.11.059. DOI: 10.1016/j.cell.2016.11.059]. </Ref>. When MRAS binds GTP, it becomes active, which allows MRAS to bind the rest of the complex<ref name="Hauseman" />. MRAS is a subvariant of the RAS protein and therefore shares most of its regulatory and effector interactions<Ref name= 'Young'>Young, L., Rodriguez-Viciana, P. MRAS: A Close but Understudied Member of the RAS Family. Cold Spring Harbor Perspectives in Medicine (2018). doi: 10.1101/cshperspect.a033621. [https://perspectivesinmedicine.cshlp.org/content/8/12/a033621.full.pdf+html. DOI: 0.1101/cshperspect.a033621]. </Ref>. While other RAS variants bind in complex with SHOC2 and | <scene name='95/952705/Mras_structure/4'>MRAS</scene> is a monomeric GTPase and is anchored in the cell membrane by a C-terminal S-Farnesyl cysteine carboxylmethyl ester <Ref name='Zhou'> Zhou, Y., Prakash, P., Liang, H., et al. Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output. Cell, 168(1-2), 239–251.e16 doi: 10.1016/j.cell.2016.11.059. [https://doi.org/10.1016/j.cell.2016.11.059. DOI: 10.1016/j.cell.2016.11.059]. </Ref>. When MRAS binds GTP, it becomes active, which allows MRAS to bind the rest of the complex<ref name="Hauseman" />. MRAS is a subvariant of the RAS protein and therefore shares most of its regulatory and effector interactions<Ref name= 'Young'>Young, L., Rodriguez-Viciana, P. MRAS: A Close but Understudied Member of the RAS Family. Cold Spring Harbor Perspectives in Medicine (2018). doi: 10.1101/cshperspect.a033621. [https://perspectivesinmedicine.cshlp.org/content/8/12/a033621.full.pdf+html. DOI: 0.1101/cshperspect.a033621]. </Ref>. While other RAS variants bind in complex with SHOC2 and PP1C to allow it to have phosphatase activity, MRAS binds the tightest. | ||
===Switch I and II=== | ===Switch I and II=== | ||
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=Implications= | =Implications= | ||
[[Image: | [[Image:Screenshot 2023-04-17 at 2.43.15 PM.png|500px|right|thumb|<font size="2"><div style="text-align: center;">'''Figure 4'''. Common Symptoms of Noonan Syndrome. </div></font>]] | ||
The SHOC2-PP1C-MRAS complex's key role in the regulation of the MAPK-RAF pathway means that minor changes in its structure or function can have drastic biological consequences. Unregulated activation of the MAPK pathway is the cause of several human cancers due to unchecked cell division and proliferation<ref name="Kwan" />. Mutations that stabilize the interactions of the SMP complex enhance PP1C phosphatase activity <Ref name="Jajian" />, leading to increased RAF signaling and accelerated cell division. Most SHOC2 or PP1C mutations alter residues that are the direct contact points, stabilizing the interaction between the two proteins. Mutations to MRAS result in persistent binding of GTP, leading to consistent activation of the cell signaling pathway<ref name="Kwan" />. | The SHOC2-PP1C-MRAS complex's key role in the regulation of the MAPK-RAF pathway means that minor changes in its structure or function can have drastic biological consequences. Unregulated activation of the MAPK pathway is the cause of several human cancers due to unchecked cell division and proliferation<ref name="Kwan" />. Mutations that stabilize the interactions of the SMP complex enhance PP1C phosphatase activity <Ref name="Jajian" />, leading to increased RAF signaling and accelerated cell division. Most SHOC2 or PP1C mutations alter residues that are the direct contact points, stabilizing the interaction between the two proteins. Mutations to MRAS result in persistent binding of GTP, leading to consistent activation of the cell signaling pathway<ref name="Kwan" />. | ||
