Practice question

Ras small GTPases H-Ras, N-Ras, K-Ras are central hubs in growth factor signaling linking receptor tyrosine kinases to Raf-MEK-ERK MAPK cascade regulating proliferation, differentiation, survival and cytoskeletal remodeling. For signaling competence Ras must associate with inner leaflet of plasma membrane where it interacts with effectors. This localization depends on C-terminal CAAX prenylation. H-Ras, N-Ras, K-Ras4A undergo farnesylation of CAAX cysteine by farnesyltransferase forming thioether linked 15-carbon anchor, followed by RCE1 cleavage and ICMT methylation. Additional second signal provided by palmitoylation of upstream cysteines for H-Ras and N-Ras or polybasic stretch for K-Ras4B enhances stable membrane binding and partitioning to distinct microdomains. GPI anchoring attaches extracellularly and myristoylation occurs at N-terminal glycine, not relevant to Ras, which is prenylated C-terminally. Oncogenic mutations lock Ras GTP-bound active causing constitutive signaling, making membrane association via farnesylation crucial therapeutic target for inhibitor development in cancer biology. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.