Sandbox Reserved 1790: Difference between revisions
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Mutations affecting SMP complex formation and stability can increase or decrease MAPK signaling, where increased stability of the complex increases MAPK signaling while decreased stability decreases signaling <ref name="Liau" />. There are a set of mutations that can happen on the SMP complex as a whole that can cause [https://www.mayoclinic.org/diseases-conditions/noonan-syndrome/symptoms-causes/syc-20354422. Noonan syndrome], a rasopathy disorder <ref name="Liau" />. On SHOC2, if the following mutations S2G, C260Y, and P510L caused differences in the complex formation with PP1C <ref name="Liau" />. On PP1C, the mutation P50R resulted in stronger ionic interactions with residues on SHOC2, resulting in a more stabilized complex <ref name="Liau" />. On MRAS, mutations such as G23V and T681I, can increase the proportion of MRAS that is GTP bound, which results in increased affinity in the SMP complex overall <ref name="Liau" />. If these mutations happen all at once, or just one or two at a time, it can still significantly alter the functionality of the SMP complex <ref name="Liau" />. This can lead to diseases like Noonan syndrome, which is where there are developmental and growth issues, and can even lead to cancers <ref name="Liau" />. | Mutations affecting SMP complex formation and stability can increase or decrease MAPK signaling, where increased stability of the complex increases MAPK signaling while decreased stability decreases signaling <ref name="Liau" />. There are a set of mutations that can happen on the SMP complex as a whole that can cause [https://www.mayoclinic.org/diseases-conditions/noonan-syndrome/symptoms-causes/syc-20354422. Noonan syndrome], a rasopathy disorder <ref name="Liau" />. On SHOC2, if the following mutations S2G, C260Y, and P510L caused differences in the complex formation with PP1C <ref name="Liau" />. On PP1C, the mutation P50R resulted in stronger ionic interactions with residues on SHOC2, resulting in a more stabilized complex <ref name="Liau" />. On MRAS, mutations such as G23V and T681I, can increase the proportion of MRAS that is GTP bound, which results in increased affinity in the SMP complex overall <ref name="Liau" />. If these mutations happen all at once, or just one or two at a time, it can still significantly alter the functionality of the SMP complex <ref name="Liau" />. This can lead to diseases like Noonan syndrome, which is where there are developmental and growth issues, and can even lead to cancers <ref name="Liau" />. | ||
[[Image: | [[Image:Complex.png|800 px|thumb|center|'''Figure 3:'''Signaling cascade is shown with SHOC2 (magenta), PP1C (blue), and MRAS (white). SHOC2 binds to PP1C then to MRAS at the cell membrane. The SMP complex is now oriented near the membrane bound RAF complex (green). ]] | ||
[[Image:Dephosphorylation.jpg|600 px|thumb|center|'''Figure 4:'''PP1C dephosphorylates RAF protein at serine 259 ]] | [[Image:Dephosphorylation.jpg|600 px|thumb|center|'''Figure 4:'''PP1C dephosphorylates RAF protein at serine 259 ]] | ||