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Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering.

Sci Rep. 2016-08; 
BlaževitšOlga,MideksaYonatan G,ŠolmanMaja,LigabueAlessio,AriottiNicholas,NakhaeizadehHossein,FansaEyad K,PapageorgiouAnastassios C,WittinghoferAlfred,AhmadianMohammad R,AbankwaDa
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摘要

Galectin-1 (Gal-1) dimers crosslink carbohydrates on cell surface receptors. Carbohydrate-derived inhibitors have been developed for cancer treatment. Intracellularly, Gal-1 was suggested to interact with the farnesylated C-terminus of Ras thus specifically stabilizing GTP-H-ras nanoscale signalling hubs in the membrane, termed nanoclusters. The latter activity may present an alternative mechanism for how overexpressed Gal-1 stimulates tumourigenesis. Here we revise the current model for the interaction of Gal-1 with H-ras. We show that it indirectly forms a complex with GTP-H-ras via a high-affinity interaction with the Ras binding domain (RBD) of Ras effectors. A computationally generated model of the Gal... More

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