🧬 The MAPK/ERK Signaling Cascade

About this simulation

A growth-factor ligand binds a receptor tyrosine kinase (RTK) on the cell membrane, causing it to dimerize and autophosphorylate. This recruits adaptor proteins that switch the small GTPase Ras into its active, GTP-bound state. Active Ras recruits Raf to the membrane, which phosphorylates MEK, which in turn phosphorylates ERK. Active ERK translocates into the nucleus and phosphorylates transcription factors that switch on genes controlling cell growth, division and differentiation.

How it works

• Each kinase in the relay is itself an enzyme, so one active receptor can activate many Ras molecules, each active Raf can activate many MEK molecules, and so on — a small input signal is amplified in successive stages.
• Glowing pulses travel down the pathway tube from one node to the next; the number of pulses leaving a node multiplies by the amplification factor, visualising signal gain.
• Each node brightens as pulses arrive and fades as it is dephosphorylated by cellular phosphatases, keeping the signal transient rather than permanent.
• With feedback enabled, active ERK loops back to dampen receptor/Raf activity — the mechanism that produces pulsed or oscillatory (rather than constant) ERK activity in real cells.

Controls

• Ligand concentration — how much growth factor is bound to receptors; drives how often new pulses are triggered.
• Amplification per step — how strongly each kinase stage multiplies the number of downstream pulses.
• Cascade speed — how fast pulses travel along the pathway.
• ERK negative feedback — toggles ERK-driven inhibition of upstream signalling, producing damped oscillations instead of a steady glow.
• ↺ Reset cascade — clears all in-flight pulses. Drag to rotate, scroll to zoom.

Did you know?

Mutations that lock Ras or Raf (e.g. KRAS G12D, BRAF V600E) in their "always-on" state are among the most common drivers of human cancer, because they keep this proliferation signal switched on regardless of receptor input.