📡 Cell Signaling — MAPK/ERK Cascade
A growth factor binds a receptor tyrosine kinase, activating Ras → Raf → MEK → ERK. Each step amplifies the signal: one activated receptor can trigger thousands of ERK molecules. Negative feedback from ERK prevents sustained activation — a key feature that converts graded input into sharp digital (switch-like) responses.
How the MAPK Cascade Works
When a growth factor (e.g. EGF) binds its receptor (EGFR), the receptor dimerises and auto-phosphorylates. This recruits adapter protein Grb2 and SOS, catalysing GDP→GTP exchange on Ras. Active Ras-GTP recruits Raf to the membrane, where Raf phosphorylates MEK, which in turn doubly-phosphorylates ERK.
Active ERK enters the nucleus and phosphorylates transcription factors driving cell proliferation. It also phosphorylates SOS (negative feedback), curbing its own activation. The scaffold protein KSR organises all three kinases, dramatically increasing efficiency. Move the sliders to see ultrasensitivity (switch-like response) emerge from cooperative ERK activation.