Sandbox Reserved 1710: Difference between revisions
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== Function == | == Function == | ||
[[Image:mechanismofRas.png|500 px|left|thumb|Figure 2: Mechanism of Ras Regulation by Neurofibromin. One chain of the homodimer is represented in cyan with its important domains highlighted. Ras Guanine Nucleotide Exchange Factors (RasGEFs) are shown catalyzing the transition from an active to an inactive Ras molecule and Neurofibromin is shown catalyzing the reverse reaction]] | [[Image:mechanismofRas.png|500 px|left|thumb|Figure 2: Mechanism of Ras Regulation by Neurofibromin. One chain of the homodimer is represented in cyan with its important domains highlighted. Ras Guanine Nucleotide Exchange Factors (RasGEFs) are shown catalyzing the transition from an active to an inactive Ras molecule and Neurofibromin is shown catalyzing the reverse reaction]] | ||
Neurofibromin functions as a tumor suppressor protein.<ref name="Trovó-Marqui">PMID:16813595</ref> It prevents cell growth by turning off [https://en.wikipedia.org/wiki/Ras_GTPase Ras] which in its active state, stimulates cell growth and division (Figure 2). Ras is a small, monomeric [https://en.wikipedia.org/wiki/GTPase GTPase] that binds to GTP and hydrolyzes it to GDP. When Ras is active, it subsequently activates other proteins that stimulate cell growth and proliferation. Ras is membrane-bound and interacts with Neurofibromin, a cytoplasmic protein, in the open conformation of Neurofibromin. Neurofibromin is brought to the membrane to associate with Ras by [https://en.wikipedia.org/wiki/SPRED1 SPRED1]. [https://medlineplus.gov/genetics/gene/spred1/ SPRED1] is a protein that helps regulate the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway Ras/MAPK signaling pathway] responsible for the growth and proliferation of cells. Binding of SPRED1 to [https://en.wikipedia.org/wiki/RAF_kinase Raf] in the MAPK signaling pathway blocks the activation of Raf, halts the rest of the pathway, and stops cell growth and proliferation. Unlike Ras, Neurofibromin can interact with SPRED1 in both the open and closed conformations.<ref name="Naschberger">PMID:34707296</ref> The interaction between Neurofibromin and Ras is activated via an [https://en.wikipedia.org/wiki/Arginine_finger Arginine finger] (Arg 1276) present in the GRD domain of Neurofibromin. Arg 1276 is only accessible for binding when the GRD and Sec14-PH domains are rotated into the open conformation. Ras binds to the arginine finger of Neurofibromin with its switch regions 1 and 2.<ref name="Trovó-Marqui">PMID:16813595</ref When Arg 1276 is able to associate with Ras, Neurofibromin downregulates the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway Ras signaling pathway] by speeding up Ras's GTPase activity, hydrolyzing the GTP associated with Ras to GDP. In its GDP bound state, Ras is inactive and cell growth and division is inhibited. <ref name="Naschberger">PMID:34707296</ref> | Neurofibromin functions as a tumor suppressor protein.<ref name="Trovó-Marqui">PMID:16813595</ref> It prevents cell growth by turning off [https://en.wikipedia.org/wiki/Ras_GTPase Ras] which in its active state, stimulates cell growth and division (Figure 2). Ras is a small, monomeric [https://en.wikipedia.org/wiki/GTPase GTPase] that binds to [https://en.wikipedia.org/wiki/Guanosine_triphosphate GTP] and hydrolyzes it to [https://en.wikipedia.org/wiki/Guanosine_diphosphate GDP]. When Ras is active, it subsequently activates other proteins that stimulate cell growth and proliferation. Ras is membrane-bound and interacts with Neurofibromin, a cytoplasmic protein, in the open conformation of Neurofibromin. Neurofibromin is brought to the membrane to associate with Ras by [https://en.wikipedia.org/wiki/SPRED1 SPRED1]. [https://medlineplus.gov/genetics/gene/spred1/ SPRED1] is a protein that helps regulate the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway Ras/MAPK signaling pathway] responsible for the growth and proliferation of cells. Binding of SPRED1 to [https://en.wikipedia.org/wiki/RAF_kinase Raf] in the MAPK signaling pathway blocks the activation of Raf, halts the rest of the pathway, and stops cell growth and proliferation. Unlike Ras, Neurofibromin can interact with SPRED1 in both the open and closed conformations.<ref name="Naschberger">PMID:34707296</ref> The interaction between Neurofibromin and Ras is activated via an [https://en.wikipedia.org/wiki/Arginine_finger Arginine finger] (Arg 1276) present in the GRD domain of Neurofibromin. Arg 1276 is only accessible for binding when the GRD and Sec14-PH domains are rotated into the open conformation. Ras binds to the arginine finger of Neurofibromin with its switch regions 1 and 2.<ref name="Trovó-Marqui">PMID:16813595</ref When Arg 1276 is able to associate with Ras, Neurofibromin downregulates the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway Ras signaling pathway] by speeding up Ras's GTPase activity, hydrolyzing the GTP associated with Ras to GDP. In its GDP bound state, Ras is inactive and cell growth and division is inhibited. <ref name="Naschberger">PMID:34707296</ref> | ||
