The ERK Cascade As a Prototype of MAPK Signaling Pathways

Sequential activation of kinases (protein kinase cascades) is a common mechanism of signal transduction in many cellular processes (1 ). Over the past decade several related intracellular signaling cascades have been elucidated, collectively known as mitogen-activated protein kinase (MAPK) signaling cascades (2 –7 ). These cascades cooperate in transmitting extracellular signals to their intracellular targets and thus initiate cellular processes such as proliferation, differentiation, development, stress response, and apoptosis. Each of these signaling cascades consists of three to six tiers of protein kinases that sequentially activate each other by phosphorylation. The similarity between the enzymes that comprise each tier in the various cascades makes them a part of a superfamily of protein kinases.