In the mitogen activated protein kinase pathway, the activation of RAS is counteracted by-

RAS protein is a signal transducing protein. Signal transducing proteins receive growth signals from outside the cell and transmit it to the nucleus. Normally RAS proteins are attached to the cytoplasmic aspect of the plasma membrane where they keep on converting between an active signal transmitting state and an inactive quiescent state. In the inactive state, the RAS proteins bind Guanosine diphosphate (GDP). When the cells are stimulated by growth factors or other receptor - ligand interactions, RAS becomes activated by exchanging GDP for GTP. This activates RAS then recruits raf - 1 and activates MAP-kinase pathway. The MAP kinases so activated target nuclear transcription factors and then they promote mitogenesis. The net result of this pathway is activation of protein phosphorylation cascade which amplifies the signal and stimulates quiescent cells to enter the growth cycle. In the normal cells the activated state of this RAS protein is transient because the normal RAS proteins have intrinsic GTPase activity. This GTPase activity hydrolyzes GTP to GDP and thus returns the RAS protein to its normal quiescent stage. Now, what is the role of GTPase activating proteins, (GAPS) in this pathway. The GTPase activating protien (GAPS) significantly accelarates the intrinsic GTPase activity of the active RAS protein. The (GAPs) bind to the active RAS and augment its GTPase activity by more than 1000 fold leading to rapid hydrolysis of GTP back to GDP. Thus GAPs function as brakes that prevents uncontrolled RAS activity. Mutation of the RAS protein causes cancer. Mutation in the RAS protein causes permanent activation of the RAS protein. The mutant RAS protein can bind to GAP but their GTPase activity fails to be augumented. Therefore the mutant RAS proteins are trapped in their excited GTP bound form. This causes pathological activation of mitogenic signalling pathway leading to continuous stimulation of cells without any external trigger. Cancers associated with RAS protein - Ca lung   Ca pancreas  Ca colon      Leukemias         Point mutation of RAS family genes is the single most common abnormality of oncogenes in human tumor.