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Abstract

Rat sarcoma viral oncogene homolog (Ras) proteins are important signaling molecules ubiquitously expressed in eukaryotes and are key regulators of normal proliferation and differentiation. The Ras family is a group of small GTPases that reside on the membrane and are involved in multiple cell signaling cascades.They transmit growth signals from cell surface receptors, such as tyrosine kinase receptors, by switching between GTP or GDP bound states. Ras is inactive when GDP bound, but stimulation by upstream factors results in the exchange of GDP for GTP with the aid of guanine exchange factors (GEFs). GTP bound Ras is able to bind and recruit downstream electors to the membrane. Although Ras is able to hydrolyze GTP to GDP, the endogenous reaction is slow and is catalyzed by GTPase-activating proteins (GAPs). A third of all human cancers have a constitutively active Ras mutation, making Ras one of the most frequently mutated oncogenes. Oncogenic Ras mutations are single base substitutions that stabilize GTP-bound state which results in constitutive activation of Ras and its target proteins, leading to several hallmarks of cancer.

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