Figure 1. Organization of mammalian and yeast MAPK pathways. Note the high degree of organizational conservation. The dotted lines represent structural homologies (as high as 45% in the protein kinase catalytic domains between the yeast and mammalian homologues). The yeast Ste5 protein acts as a scaffold to physically organize and insulate the components.

Figure 2. The three major mammalian MAPK pathways. In addition to the mitogen-induced pathway, the SAPK/JNK and p38 MAPK pathways share organizational similarities but respond primarily to cellular stresses. The dotted lines reflect structural relatedness. The shading represents the molecules that bind to the JIP1 scaffolding protein. Note, many of the targets of these pathways regulate gene transcription.

Figure 3. The phosphatidylinositol 3¢ kinase pathway. (a) In resting cells, the membrane levels of PIP3 (3¢,4¢,5¢-phosphatidylidylinositol) are very low, PI3¢K and PKB are cytoplasmic and inactive. (b) Upon ligand-induced dimerization/activation of receptor-tyrosine kinases (RTKs), PI3¢K is recruited to the newly tyrosine phosphorylated receptors juxtaposing the enzyme with its substrate. The resulting PIP3 attracts PKB and two activating protein kinases, PDK1 and PDK2, to the membrane via PH domains whereupon PKB is activated via phosphorylation. The activated enzyme then diffuses into the cytoplasm and nucleus to interact with its substrates.

Figure 4. The Wnt signalling pathway. (a) In resting cells, the protein kinase, GSK-3, binds the scaffolding protein, Axin, which also binds APC and -catenin. Since the kinase activity of GSK-3 is high in unstimulated cells, -catenin is phosphorylated which targets it for degradation, resulting in suppression of its concentration. (b) When the pathway is stimulated, GSK-3 activity is inhibited, relieving phosphorylation of -catenin, thus allowing it to accumulate and interact with the LEF1/TCF transcription factor. (c) In certain cancer cells, APC is lost, disconnecting the pathway and leading to accumulation of -catenin in the absence of signal. In other cancer cells, -catenin itself can be mutated to a stabilized form. (d) The pathway is remarkably conserved in fruit flies where the homologue of GSK-3 and -catenin are termed Zeste-White 3 and Armadillo, respectively.