The Ras/MAP Kinase Pathway
Ras is an intracellular GTPase switch protein that acts downstream from most RTKs and cytokine receptors. Like Gα, Ras cycles between an inactive GDP-
RTKs are linked indirectly to Ras via two proteins: GRB2, an adapter protein, and Sos, which has GEF activity (see Figure 16-21).
The SH2 domain in GRB2 binds to a phosphotyrosine in activated RTKs, while its two SH3 domains bind Sos, thereby bringing Sos close to membrane-
Binding of Sos to inactive Ras causes a large conformational change that permits release of GDP and binding of GTP, forming active Ras (see Figure 16-23).
Activated Ras triggers a kinase cascade in which Raf, MEK, and MAP kinase are sequentially phosphorylated and thus activated. Activated MAP kinase then translocates to the nucleus (see Figure 16-24).
Activation of MAP kinase following stimulation of a growth-
Different extracellular signals induce activation of different MAP kinase pathways, which regulate diverse cellular processes by phosphorylating different sets of transcription factors.
The kinase components of each MAP kinase cascade assemble into a large pathway-