Sandbox Reserved 1767: Difference between revisions
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===Auto-inhibition=== | ===Auto-inhibition=== | ||
[[Image:MECH.png| | [[Image:MECH.png|500 px|center|thumb|Figure 3: Mechanism of SMP complex formation and activation of RAF.<ref name="Liau">PMID: 35768504</ref>.]] | ||
The Ras-Raf signaling cascade will be inhibited without the dephosphorylation of Raf at Ser259. There is a <scene name='95/952695/14-3-3/1'>14-3-3</scene> dimer present in the cytoplasm that interacts with Raf through hydrogen bonds between R129 of 14-3-3 and Ser259 of Raf when Ser259 is phosphorylated. This interaction causes an <scene name='95/952695/Autoinhibited_confirmation/7'>autoinhibited confirmation</scene> as 14-3-3 restricts Raf to the cytoplasm and sterically inhibits Raf from binding with activated Ras. This interaction is crucial in regulating cell proliferation, as it prevents cell growth in the absence of a signal. Extracellular growth factors trigger GTP to bind to MRAS, which triggers SMP formation. Upon SMP complex formation, PP1C is brought into close proximity of Ras, leading to the dephosphorylation of Ser259 of Raf by the active site of PP1C. Once dephosphorylated, Raf is in the <scene name='95/952695/Non-inhibited_confirmation/9'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref> | The Ras-Raf signaling cascade will be inhibited without the dephosphorylation of Raf at Ser259. There is a <scene name='95/952695/14-3-3/1'>14-3-3</scene> dimer present in the cytoplasm that interacts with Raf through hydrogen bonds between R129 of 14-3-3 and Ser259 of Raf when Ser259 is phosphorylated. This interaction causes an <scene name='95/952695/Autoinhibited_confirmation/7'>autoinhibited confirmation</scene> as 14-3-3 restricts Raf to the cytoplasm and sterically inhibits Raf from binding with activated Ras. This interaction is crucial in regulating cell proliferation, as it prevents cell growth in the absence of a signal. Extracellular growth factors trigger GTP to bind to MRAS, which triggers SMP formation. Upon SMP complex formation, PP1C is brought into close proximity of Ras, leading to the dephosphorylation of Ser259 of Raf by the active site of PP1C. Once dephosphorylated, Raf is in the <scene name='95/952695/Non-inhibited_confirmation/9'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref> | ||
