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Another Ras effector is the GEPs family (RalGDS,c RGL, and RIf/RGL2) that serve

ID: 200781 • Letter: A

Question

Another Ras effector is the GEPs family (RalGDS,c RGL, and RIf/RGL2) that serve as activators of the Ral small monomeric GTPases (Wolthuis and Bos, 1999; a Danen and Yamada, 2001). RAL-GTP activates the n phospholipase D (PLD) that, by hydrolyzing phosphati- ( dilcolines, generates satures and monoinsatures phos- r phatidates, which are putative activator molecules of g Rho. RAL also seems to interact with a Cdc42 and RAC C GAP (Hodgkin et al., 1998). Rho, RAC, and Cdc42 1 constitute another family of monomeric G proteins that r play an important role in cytoskeleton remodeling and activate the kinases regulating the activity of various e transcriptional factors. It has been shown recently that Rho represses expression of a cyclins inhibitor p21 (Olson et al., 1998) The third Ras effector is the phosphatidylinositol 3-kinase (PI3-K). Ras-GTP can bind and activate the catalytic subunit of this enzyme that generates PI(3,4,5)P3 by phosphorylation the PI(4,5)P2 in 3- position. The PI(3,4,5)P3 acts directly like a second 1 messenger, binding several cytoskeleton kinase pro- teins and modulating the activity by conformational changes and/or their membrane translocation. PKB/ AKT is an enzyme indirectly activated by PI3-K, which inactivates BAD, pro-apoptotic factor, by phophoryla- tion (Downward, 1998)

Explanation / Answer

GEF's family(RalGDS, RGL, Rlf/RGL2) play the role of Ras effectors which helps in activating Ral small monomeric GTPase. Phospholipase D(PLD) is activated by RAL-GTP by hydrolyzing phosphatidates, which generates satures and monoinsatures phosphatidates, which are considered to be activator molecules of Rho. It has been seen that RAL also interactswith Cdc41 and RAC GAP.

The monomeric G proteins family which constitute Rho, RAC and Cdc42 plays an important role in cytoskeleton remodelling and also activates the kinases which regulates the activity of various transcriptional factors. Recently it has been shown that Rho represses the expression of cyclins inhibitor p21waf1.

The third Ras effector called the phosphatidylinisitol 3-kinase, which gets activated when Ras-GTP binds and the catalytic subunit is activated which generates PI(3,4,5)P3 by phosphorylation of the PI(4,5)P2 in 3 position. The PI(3,4,5)P3 acts directly like a seocnd messenger, which binds several cytoskeleton kinase proteins and modulates the activity by conformational changed or/and by membrane translocation. PI3-K activates the enzyme PKB/AKT indirectly. PKB/AKT inactivates BAD, pro-apoptotic factor, by phosphorylation.  

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