Sandbox Reserved 1767: Difference between revisions
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[[Image:MECH.png|700 px|center|thumb|'''Figure 1''': Mechanism of SMP complex formation and activation of RAF.<ref name="Liau">PMID: 35768504</ref><ref name="Lavoie">PMID: 35970881</ref>]] | [[Image:MECH.png|700 px|center|thumb|'''Figure 1''': Mechanism of SMP complex formation and activation of RAF.<ref name="Liau">PMID: 35768504</ref><ref name="Lavoie">PMID: 35970881</ref>]] | ||
The RAS-RAF signaling cascade is inhibited when RAF is phosphorylated at Ser259.<ref name="Kwon">PMID: 35831509</ref> 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 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005716/. 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/9'>autoinhibited confirmation</scene> as 14-3-3 restricts RAF to the cytoplasm and sterically inhibits RAF from binding with RAS. This interaction is crucial in regulating [https://us.progen.com//Antibodies/Research-Area/Cell-Cycle-Proliferation/ cell proliferation], as it prevents cell growth in the absence of a signal. [https://www.ncbi.nlm.nih.gov/books/NBK26877/#:~:text=Extracellular%20Growth%20Factors%20Stimulate%20Cell,Cell%20Growth%2C%20Cell%20Division%2C%20and Extracellular Growth Factors] cause GTP to bind to MRAS which triggers SMP formation <ref name="Lavoie">PMID: 35970881</ref>.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 <ref name="Lavoie">PMID: 35970881</ref>. Once dephosphorylated, RAF is in the | The RAS-RAF signaling cascade is inhibited when RAF is phosphorylated at Ser259.<ref name="Kwon">PMID: 35831509</ref> 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 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005716/. 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/9'>autoinhibited confirmation</scene> as 14-3-3 restricts RAF to the cytoplasm and sterically inhibits RAF from binding with RAS. This interaction is crucial in regulating [https://us.progen.com//Antibodies/Research-Area/Cell-Cycle-Proliferation/ cell proliferation], as it prevents cell growth in the absence of a signal. [https://www.ncbi.nlm.nih.gov/books/NBK26877/#:~:text=Extracellular%20Growth%20Factors%20Stimulate%20Cell,Cell%20Growth%2C%20Cell%20Division%2C%20and Extracellular Growth Factors] cause GTP to bind to MRAS which triggers SMP formation <ref name="Lavoie">PMID: 35970881</ref>.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 <ref name="Lavoie">PMID: 35970881</ref>. Once dephosphorylated, RAF is in the | ||
<scene name='95/952695/Non-inhibited_confirmation/ | <scene name='95/952695/Non-inhibited_confirmation/11'>active confirmation</scene>, allowing RAS to bind RAF, initiating the signaling cascade.<ref name="Young">PMID: 30348783</ref> | ||
== Structure of Subunits == | == Structure of Subunits == | ||