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11.1.07Review - Review 10.25.07 P13#1 2 p14#5 8 p15#2...

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Review 10.25.07 P13#1, 2, p14#5, 8, p15#2 p17#11 Review 11/2/06 #3,#4 Review 11/9/06 #1,3,4 P13#1 A guanyl exchange factor (GEF) binds to RAS and facilitates exchange of GTP for GDP making GTP-RAS. GTP-RAS is the active form of RAS which directly binds to and activates RAF, its downstream effector (it’s a protein kinase). Mutations in RAS that prevent GTP-hydrolysis or binding to GTPase Activating Protein (GAP) make RAS persistently GTP bound and thus persistently active. A persistently active RAS results in persistent activation of Ras signaling pathways, which is oncogenic. P13#2 To test the role of a protein in a pathway, mimic /stimulate and inhibit the protein. Rita Levi-Montalcini mimicked the effect of the tumor by implanting an NGF soaked sponge into the embryo, and observed the large DRGs (dorsal root ganglions) and axons growing toward the sponge just as they had with the tumor. This suggested that NGF was the active substance released from the tumor and effects neuronal development. RL-M inhibited the NGF effect by adding antiNGF antibodies to embryo’s with tumors. The antibody prevented the effect of the tumor, and led to elimination of the DRGs. This supported the idea that NGF was a biologically relevant substance affecting axon growth and neuronal survival.
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