Sandbox Reserved 1767: Difference between revisions
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==RAS== | ==RAS== | ||
RAS proteins are GTP-dependent intracellular switches that are anchored to the plasma membrane. .<ref name="Liau">PMID: 35768504</ref> RAS proteins activate RAF kinases through direct binding and membrane recruitment, resulting in RAF dimerization and pathway activation. <ref name="Liau">PMID: 35768504</ref>. The SMP complex has specificity for MRAS. Other RAS proteins may bind to SHOC2, but MRAS induces the complex formation with a significantly lower Kd (dissociation constant).<ref name="Liau">PMID: 35768504</ref> There are no known membrane interacting regions on SHOC2 and PP1C, meaning the hydrophobic fatty acid tail on MRAS is responsible for recruiting the complex to the cell membrane .<ref name="Hauseman">PMID:35830882</ref>. | RAS proteins are GTP-dependent intracellular switches that are anchored to the plasma membrane. .<ref name="Liau">PMID: 35768504</ref> RAS proteins activate RAF kinases through direct binding and membrane recruitment, resulting in RAF dimerization and pathway activation. <ref name="Liau">PMID: 35768504</ref>. The SMP complex has specificity for MRAS. Other RAS proteins may bind to SHOC2, but MRAS induces the complex formation with a significantly lower Kd (dissociation constant).<ref name="Liau">PMID: 35768504</ref> There are no known membrane interacting regions on SHOC2 and PP1C, meaning the hydrophobic fatty acid tail on MRAS is responsible for recruiting the complex to the cell membrane .<ref name="Hauseman">PMID:35830882</ref>. | ||
A significant amount of steric overlap is seen in MRAS for the binding sites of PP1C, SHOC2, and Raf. In figure 1, MRAS is shown in green, with the SHOC2 binding site colored cyan, the PP1C binding site colored green, and the RAF binding site shown in red on a different RAS protein. Hence, multiple RAS proteins are required for further activation of the receptor tyrosine kinase pathway. Due to the significant overlap in binding domains, one MRAS molecule is needed to recruit SHOC2 and PP1C to the membrane, and another RAS molecule is needed activate RAF. The ability of MRAS-GTP to cluster at the cell membrane</scene> is a crucial capability for this protein complex. The presence of this<scene name='95/952695/413cellmemprotrusion/4'>palmitoylated tail</scene> is responsible for this anchoring to the cell membrane, similar to the hydrophobic fatty acid tail on MRAS that is responsible for recruiting SMP to the cell membrane, allowing only for 2D movement and increasing local concentrations of the players needed in this signaling pathway. .<ref name="Hauseman">PMID:35830882</ref> | A significant amount of steric overlap is seen in MRAS for the binding sites of PP1C, SHOC2, and Raf. In figure 1, MRAS is shown in green, with the SHOC2 binding site colored cyan, the PP1C binding site colored green, and the RAF binding site shown in red on a different RAS protein. Hence, multiple RAS proteins are required for further activation of the receptor tyrosine kinase pathway. Due to the significant overlap in binding domains, one MRAS molecule is needed to recruit SHOC2 and PP1C to the membrane, and another RAS molecule is needed activate RAF. The ability of MRAS-GTP to cluster at the cell membrane</scene> is a crucial capability for this protein complex. The presence of this <scene name='95/952695/413cellmemprotrusion/4'>palmitoylated tail</scene> is responsible for this anchoring to the cell membrane, similar to the hydrophobic fatty acid tail on MRAS that is responsible for recruiting SMP to the cell membrane, allowing only for 2D movement and increasing local concentrations of the players needed in this signaling pathway. .<ref name="Hauseman">PMID:35830882</ref> | ||