Sandbox Reserved 1767: Difference between revisions

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===Auto-inhibition===

[[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. 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/8'>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 [https://us.progen.com//Antibodies/Research-Area/Cell-Cycle-Proliferation/ 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 <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/Autoinhibited_confirmation/8'>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 is inhibited when Raf is phosphorylated 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/8'>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 [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] trigger 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/Autoinhibited_confirmation/8'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref>

== Structure of Subunits ==

Sandbox Reserved 1767: Difference between revisions

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@@ Line 13: / Line 13: @@
 ===Auto-inhibition===
 [[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. 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/8'>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 [https://us.progen.com//Antibodies/Research-Area/Cell-Cycle-Proliferation/ 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 <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/Autoinhibited_confirmation/8'>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 is inhibited when Raf is phosphorylated 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/8'>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 [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] trigger 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/Autoinhibited_confirmation/8'>active confirmation</scene>, allowing for the interaction of Ras and Raf, and the initiation of the signaling cascade.<ref name="Young">PMID: 30348783</ref>
 == Structure of Subunits ==