Sandbox Reserved 1767: Difference between revisions

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OCA, Jaime Prilusky, Kayla Wilhoite, Sloan August, Rosa Trippel, R. Jeremy Johnson

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 <scene name='95/952695/Overall_image/2'>The SHOC2-MRAS-PP1C</scene> (SMP) holophosphatase complex functions as a key regulator of the [https://www.nature.com/scitable/topicpage/rtk-14050230/#:~:text=One%20of%20the%20most%20common,anchored%20to%20the%20plasma%20membrane. receptor tyrosine kinase (RTK)] signaling pathway by removing an inhibitory phosphate on the [https://www.sciencedirect.com/science/article/pii/S0167488907001164. RAF] family of proteins to allow for [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536342/. MAPK signaling].<ref name="Kwon">PMID: 35831509</ref> This interaction of the RTK-RAS pathway and the SMP complex drives cell proliferation.<ref name="Hauseman">PMID:35830882</ref> The SMP complex is made of three subunits, SHOC2, PP1C, and MRAS. Each of these subunits has a different shape that corresponds to its different function. <scene name='95/952695/Shoc2intro/1'>The SHOC2 subunit</scene> uses a crescent shape to enhance substrate interactions and complex stability.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952695/Pp1cintro/3'>The PP1C subunit</scene> contains the the catalytic site of the complex which dephosphorylates the N-terminal phosphoserine (NTpS) of RAF.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952694/Pp1ccorrectintro/1'>The MRAS subunit</scene> binds to GTP which causes assembly of the SMP complex. The <scene name='95/952695/413cellmemprotrusion/4'>C-terminus of MRAS</scene> localizes the complex to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Once the SMP compelx is assembled, MRAS can bind to <scene name='95/952695/Raf/3'>RAF</scene>, allowing the [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000522/. signaling cascade] to continue. Mutations in one or multiple of these subunits can lead to over-activation of the signaling pathway, which may result in cancer and developmental disorders called [https://kidshealth.org/en/parents/rasopathies.html RASopathies].<ref name="Kwon">PMID: 35831509</ref>
-There are many regulatory mechanisms that serve as a lock on this [https://www.cancer.gov/research/key-initiatives/ras/about#:~:text=RAS%20proteins%20are%20important%20for,inactive%20(GDP%20form)%20states. RAS]-[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536342/. MAPK] pathway, decreasing the likelihood of unintentional pathway activation. <ref name="Hauseman">PMID:35830882</ref> One example is <scene name='95/952695/14-3-3/1'>14-3-3</scene>, a protein dimer that keeps inactive RAF localized to the cytoplasm. An <scene name='95/952695/Raf_ntps/1'>N-terminal phosphorylated serine</scene> (NTpS) keeps RAF bound to this protein dimer, and when the SMP complex is assembled, the catalytic subunit, PP1C, removes the phosphate group from the serine residue, releasing RAF from <scene name='95/952695/14-3-3/1'>14-3-3</scene>, and activating the RAS-MAPK cell proliferation pathway. <ref name="Hauseman">PMID:35830882</ref>
+There are many regulatory mechanisms that serve as a lock on this [https://www.cancer.gov/research/key-initiatives/ras/about#:~:text=RAS%20proteins%20are%20important%20for,inactive%20(GDP%20form)%20states. RAS]-[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536342/. MAPK] pathway, decreasing the likelihood of unintentional pathway activation. <ref name="Hauseman">PMID:35830882</ref> One example is <scene name='95/952695/14-3-3/1'>14-3-3</scene>, a protein dimer that keeps inactive RAF localized to the cytoplasm. An <scene name='95/952695/Raf_ntps/1'>N-terminal phosphorylated serine</scene> (NTpS) keeps RAF bound to this protein dimer, and when the SMP complex is assembled, the catalytic subunit, PP1C, removes the phosphate group from Ser259, releasing RAF from <scene name='95/952695/14-3-3/1'>14-3-3</scene>, and activating the RAS-MAPK cell proliferation pathway. <ref name="Hauseman">PMID:35830882</ref>
 In all images and animations, {{Font color|cyan|SHOC2}} will be shown as cyan blue, {{Font color|lime|MRAS}} as lime, and {{Font color|violet|PP1C}} as violet. Other important components involved in the function of the SMP complex include the {{Font color|salmon|14-3-3}} dimer and {{Font color|slateblue|Raf}}, which will be shown in salmon and slate-blue, respectively.