Cells communicate by detecting extracellular signals and converting them into intracellular responses through signal transduction cascades. This simulation models a receptor tyrosine kinase (RTK) pathway, where binding of a growth factor triggers a chain of protein activations that ultimately reaches the nucleus to alter gene expression.
From Receptor to Ras
When a ligand (such as EGF) binds to an RTK, it induces receptor dimerization -- two receptor molecules come together and cross-phosphorylate each other's intracellular tyrosine residues. These phosphotyrosines serve as docking sites for adaptor proteins like GRB2, which recruits the guanine nucleotide exchange factor SOS. SOS activates the small GTPase Ras by promoting the exchange of GDP for GTP.
The MAPK/ERK Cascade
- Signal Amplification: Each activated receptor can activate multiple G-proteins, each G-protein activates multiple adenylyl cyclases, and each cyclase produces many cAMP molecules -- creating massive amplification at every step.
- Phosphorylation Cascades: Active Ras recruits RAF (MAPKKK), which phosphorylates MEK (MAPKK), which phosphorylates ERK (MAPK). ERK then enters the nucleus to activate transcription factors controlling cell growth and differentiation.
- Signal Termination: GTPase activity hydrolyzes GTP back to GDP, phosphatases remove phosphate groups, and receptor internalization removes active receptors from the surface.
Why It Matters
Mutations that constitutively activate components of RTK pathways (especially Ras, which is mutated in ~30% of human cancers) are among the most common drivers of cancer. Drugs targeting these pathways -- including imatinib (BCR-ABL), erlotinib (EGFR), and vemurafenib (BRAF) -- represent major advances in precision oncology.
Category: Biochemistry & Molecular Biology — Cell signaling and growth factor pathways