Final answer:
GEFs activate RAS by triggering the exchange of GDP for GTP, leading to a signaling cascade that promotes cell proliferation. Cancer-related mutations in RAS hinder its GTPase function, causing continuous signaling and uncontrolled proliferation. This is central to oncogenesis and exemplified by the MAP-kinase cascade.
Step-by-step explanation:
Guanyl-nucleotide Exchange Factors (GEFs) are associated with the activation of small G-proteins such as RAS by facilitating the exchange of GDP for GTP, which turns the protein into an active state. In the context of the RAS protein, this activation triggers a signaling cascade involving RAF, MEK, and ERK, leading to cellular responses such as cell proliferation. If the GTPase activity of the RAS G-protein is inhibited, as is seen in certain cancers, RAS remains in an active, GTP-bound form. This inability to hydrolyze GTP to GDP results in continuous signal transduction, causing uncontrolled cell proliferation and contributing to oncogenesis. Mutations in RAS that inhibit its GTPase activity are a common feature in many cancers as this leads to persistent signaling through the MAP-kinase cascade and other proliferative pathways.
Furthermore, under normal circumstances, mitogenic signals such as EGF stimulate cellular processes through receptor tyrosine kinases, leading to controlled cell division. However, oncogene activation, by mutation or other means, can lead to unchecked proliferative signaling, emphasizing the critical role that properly regulated GTPase activity of the RAS protein plays in maintaining cellular homeostasis.