Sandbox Reserved 1766: Difference between revisions

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<scene name='95/952694/Overall_image/2'>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> When the subunits come together, the complex acts as a key regulator of the Receptor Tyrosine Kinase-Ras pathway and signaling cascade, by removing an inhibitory phosphorylation on the RAF family of proteins to increase MAPK (Mitogen-activated Protein Kinases) activity.<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>

Within the SMP complex, each subunit uses an individual structure which correlates with its function. The three subunits are SHOC2, PP1C, and MRAS. The SHOC2 subunit uses a crescent shape to enhance substrate interactions and complex stability. The PP1C subunit contains the catalytic active site of the complex. Finally, the MRAS subunit controls the SMP complex formation based on GTP activation. 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. The signaling cascade is kept from over-activating by being held in an auto-inhibited conformation. The SMP complex is responsible for removing this auto-inhibited conformation, allowing for Raf to bind to Ras. Mutations in any member of the SMP complex can lead to more frequent complex formation, ultimately leading to more, often uncontrolled, cell proliferation.<ref name="Kwon">PMID: 35831509</ref> SHOC2-PP1C-MRAS is being studied as a possible treatment target for many types of cancers.

Within the SMP complex, each subunit uses an individual structure which correlates with its function. The three subunits are SHOC2, PP1C, and MRAS. The SHOC2 subunit uses a crescent shape to enhance substrate interactions and complex stability. It is essential for the binding of the SMP complex since it engages both PP1C and MRAS.<ref name="Liau">PMID: 35768504</ref> The protein phosphatase 1 catalytic (PP1C) subunit contains the catalytic active site of the complex.<ref name="Liau">PMID: 35768504</ref> PP1C is a phosphatase enzyme that dephosphorylates the N-terminal phosphoserine (NTpS) of RAF, but PP1C cannot dephosphorylate NTpS while isolated from the SMP complex.<ref name="Liau">PMID: 35768504</ref> Finally, the MRAS subunit controls the SMP complex formation based on GTP activation. 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>

The signaling cascade is kept from over-activating by being held in an auto-inhibited conformation. The SMP complex is responsible for removing this auto-inhibited conformation, allowing for Raf to bind to Ras. Mutations in any member of the SMP complex can lead to more frequent complex formation, ultimately leading to more, often uncontrolled, cell proliferation.<ref name="Kwon">PMID: 35831509</ref> SHOC2-PP1C-MRAS is being studied as a possible treatment target for many types of cancers.

In all images and animations, SHOC2 will be shown as cyan blue, MRAS as lime, and PP1C as violet. Other important components involved in the function of the SMP complex include the 14-3-3 dimer and Raf, which will be shown in salmon and slate-blue, respectively.

Sandbox Reserved 1766: Difference between revisions

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 <scene name='95/952694/Overall_image/2'>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> When the subunits come together, the complex acts as a key regulator of the Receptor Tyrosine Kinase-Ras pathway and signaling cascade, by removing an inhibitory phosphorylation on the RAF family of proteins to increase MAPK (Mitogen-activated Protein Kinases) activity.<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>
-Within the SMP complex, each subunit uses an individual structure which correlates with its function. The three subunits are SHOC2, PP1C, and MRAS. The SHOC2 subunit uses a crescent shape to enhance substrate interactions and complex stability. The PP1C subunit contains the catalytic active site of the complex. Finally, the MRAS subunit controls the SMP complex formation based on GTP activation. 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. The signaling cascade is kept from over-activating by being held in an auto-inhibited conformation. The SMP complex is responsible for removing this auto-inhibited conformation, allowing for Raf to bind to Ras. Mutations in any member of the SMP complex can lead to more frequent complex formation, ultimately leading to more, often uncontrolled, cell proliferation.<ref name="Kwon">PMID: 35831509</ref> SHOC2-PP1C-MRAS is being studied as a possible treatment target for many types of cancers.
+Within the SMP complex, each subunit uses an individual structure which correlates with its function. The three subunits are SHOC2, PP1C, and MRAS. The SHOC2 subunit uses a crescent shape to enhance substrate interactions and complex stability. It is essential for the binding of the SMP complex since it engages both PP1C and MRAS.<ref name="Liau">PMID: 35768504</ref> The protein phosphatase 1 catalytic (PP1C) subunit contains the catalytic active site of the complex.<ref name="Liau">PMID: 35768504</ref> PP1C is a phosphatase enzyme that dephosphorylates the N-terminal phosphoserine (NTpS) of RAF, but PP1C cannot dephosphorylate NTpS while isolated from the SMP complex.<ref name="Liau">PMID: 35768504</ref> Finally, the MRAS subunit controls the SMP complex formation based on GTP activation. 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>
+The signaling cascade is kept from over-activating by being held in an auto-inhibited conformation. The SMP complex is responsible for removing this auto-inhibited conformation, allowing for Raf to bind to Ras. Mutations in any member of the SMP complex can lead to more frequent complex formation, ultimately leading to more, often uncontrolled, cell proliferation.<ref name="Kwon">PMID: 35831509</ref> SHOC2-PP1C-MRAS is being studied as a possible treatment target for many types of cancers.
 In all images and animations, SHOC2 will be shown as cyan blue, MRAS as lime, and PP1C as violet. Other important components involved in the function of the SMP complex include the 14-3-3 dimer and Raf, which will be shown in salmon and slate-blue, respectively.