Sandbox Reserved 1766: Difference between revisions

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== Introduction ==

<scene name='95/952694/Overall_image/2'>The SHOC2-MRAS-PP1C</scene> (SMP) is a 3-subunit complex essential for cell proliferation and the survival of many cancers<ref name="Hauseman">PMID:35830882</ref> and RASopathies.<ref name="Kwon">PMID: 35831509</ref> The SMP holophosphatase complex functions as a key regulator of the receptor tyrosine kinase (RTK) signaling pathway by removing an inhibitory phosphate on the RAF family of proteins to allow for 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='95/952694/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='95/952694/Pp1cintro/2'>The PP1C subunit</scene> is a phosphatase, and it contains the catalytic site of the complex which dephosphorylates the N-terminal phosphoserine (NTpS) of RAF green link here.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952694/Pp1ccorrectintro/1'>The MRAS subunit</scene> binds to GTP which triggers assembly of the SMP complex. The C-terminus of the MRAS subunit localizes the complex to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Mutations in one or multiple of these subunits leads to over-activation of the signaling pathway, which may result in cancer and developmental disorders called RASopathies.<ref name="Kwon">PMID: 35831509</ref>

<scene name='95/952694/Overall_image/2'>The SHOC2-MRAS-PP1C</scene> (SMP) is a 3-subunit complex essential for cell proliferation and the survival of many cancers<ref name="Hauseman">PMID:35830882</ref> and RASopathies.<ref name="Kwon">PMID: 35831509</ref> The SMP holophosphatase complex functions as a key regulator of the receptor tyrosine kinase (RTK) signaling pathway by removing an inhibitory phosphate on the RAF family of proteins to allow for 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='95/952694/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='95/952694/Pp1cintro/3'>The PP1C subunit</scene> is a phosphatase, and it contains the catalytic site of the complex which dephosphorylates the N-terminal phosphoserine (NTpS) of RAF green link here.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952694/Pp1ccorrectintro/1'>The MRAS subunit</scene> binds to GTP which triggers assembly of the SMP complex. The C-terminus of the MRAS subunit localizes the complex to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Mutations in one or multiple of these subunits leads to over-activation of the signaling pathway, which may result in cancer and developmental disorders called RASopathies.<ref name="Kwon">PMID: 35831509</ref>

There are many regulatory mechanisms that serve as a lock on this RAS-MAPK pathway, decreasing the likelihood of unintentional pathway activation. One is a protein dimer called 14-3-3 that keeps inactive RAF localized to the cytoplasm. An N-terminal phosphorylated serine 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, releasing RAF from the 14-3-3 dimer, and activating the RAS-MAPK cell proliferation pathway.

Sandbox Reserved 1766: Difference between revisions

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 == Introduction ==
-<scene name='95/952694/Overall_image/2'>The SHOC2-MRAS-PP1C</scene> (SMP) is a 3-subunit complex essential for cell proliferation and the survival of many cancers<ref name="Hauseman">PMID:35830882</ref> and RASopathies.<ref name="Kwon">PMID: 35831509</ref> The SMP holophosphatase complex functions as a key regulator of the receptor tyrosine kinase (RTK) signaling pathway by removing an inhibitory phosphate on the RAF family of proteins to allow for 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='95/952694/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='95/952694/Pp1cintro/2'>The PP1C subunit</scene> is a phosphatase, and it contains the catalytic site of the complex which dephosphorylates the N-terminal phosphoserine (NTpS) of RAF green link here.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952694/Pp1ccorrectintro/1'>The MRAS subunit</scene> binds to GTP which triggers assembly of the SMP complex. The C-terminus of the MRAS subunit localizes the complex to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Mutations in one or multiple of these subunits leads to over-activation of the signaling pathway, which may result in cancer and developmental disorders called RASopathies.<ref name="Kwon">PMID: 35831509</ref>
+<scene name='95/952694/Overall_image/2'>The SHOC2-MRAS-PP1C</scene> (SMP) is a 3-subunit complex essential for cell proliferation and the survival of many cancers<ref name="Hauseman">PMID:35830882</ref> and RASopathies.<ref name="Kwon">PMID: 35831509</ref> The SMP holophosphatase complex functions as a key regulator of the receptor tyrosine kinase (RTK) signaling pathway by removing an inhibitory phosphate on the RAF family of proteins to allow for 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='95/952694/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='95/952694/Pp1cintro/3'>The PP1C subunit</scene> is a phosphatase, and it contains the catalytic site of the complex which dephosphorylates the N-terminal phosphoserine (NTpS) of RAF green link here.<ref name="Liau">PMID: 35768504</ref> <scene name='95/952694/Pp1ccorrectintro/1'>The MRAS subunit</scene> binds to GTP which triggers assembly of the SMP complex. The C-terminus of the MRAS subunit localizes the complex to the cell membrane.<ref name="Liau">PMID: 35768504</ref> Mutations in one or multiple of these subunits leads to over-activation of the signaling pathway, which may result in cancer and developmental disorders called RASopathies.<ref name="Kwon">PMID: 35831509</ref>
 There are many regulatory mechanisms that serve as a lock on this RAS-MAPK pathway, decreasing the likelihood of unintentional pathway activation. One is a protein dimer called 14-3-3 that keeps inactive RAF localized to the cytoplasm. An N-terminal phosphorylated serine 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, releasing RAF from the 14-3-3 dimer, and activating the RAS-MAPK cell proliferation pathway.