kinase cascades

Meaning: A kinase cascade is a signal transduction pathway in which one kinase phosphorylates and activates the next kinase, which activates the next, and so on. A kinase transfers a phosphate from ATP to a serine, threonine, or tyrosine hydroxyl on its target, and the added negative charge changes the protein's shape and activity. Because each active enzyme can modify many substrate molecules, the signal is typically amplified at each step. Phosphatases remove the phosphate and shut the signal off.

On the MCAT: A passage shows a growth factor binding a receptor tyrosine kinase, then Ras, Raf, MEK, and ERK (the MAP kinase pathway), ending in transcription factor activation. You predict the effect of a change. A constitutively active kinase signals without ligand and can drive uncontrolled cell division. A loss-of-function kinase or an inhibitor blocks the steps downstream of it but not the steps upstream. A phosphatase inhibitor prolongs the signal.

Common confusion: Phosphorylation does not always activate its target; it inactivates some enzymes, such as glycogen synthase. Also keep kinase and phosphorylase apart. A kinase uses ATP to add a phosphate, whereas a phosphorylase uses inorganic phosphate to cleave a bond (glycogen phosphorylase).