FIGURE 2 The MAPK cascade initiated by insulin regulates gene expression. Binding of insulin to the insulin receptor triggers autophosphorylation, activating the protein kinase domain in the cytoplasmic region of the receptor. The tyrosine kinase phosphorylates IRS-1, activating it to bind other proteins that then phosphorylate yet other proteins, creating a cascade of protein phosphorylation events that amplifies the original signal. Numerous “middle” factors (e.g., Grb2, Sos, Ras, Raf-1, MEK, ERK, SRF), several of which are kinases, are required to transduce and amplify the original signal. The end result is phosphorylation and activation of Elk1, a transcription factor that stimulates gene expression.