Signal transduction pathways use enzymatic cascades to amplify extracellular signals. Cells often use kinase cascades to phosphorylate many downstream targets. Some cell-surface receptors, such as receptor tyrosine kinases, have cytosolic domains with kinase activity. Other receptors lack intrinsic enzymatic activity, but directly or indirectly regulate the activity of downstream enzymes. In an enzymatic cascade, the number of activated molecules increases at each step, producing an increased cellular response with few signaling ligands. For example, the MAP kinase cascade is composed of a series of kinases, such as MAP kinase, MAP kinase kinase, and MAP kinase kinase kinase, that phosphorylate other kinases. Raf can phosphorylate multiple molecules of MEK. Each activated molecule of MEK further phosphorylates multiple molecules of ERK. The ERKs then phosphorylate and activate various target molecules, including transcription factors and other kinases that promote cell growth and division.