Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.
Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals.
The molecular events linking cell surface receptors to activation of ERKs are complex.
Transgenic gene knockout mice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill some MAPK3 functions in most cells.
Activation of the ERK1/2 pathway by aberrant RAS/RAF signalling, DNA damage, and oxidative stress leads to cellular senescence.