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Figure 20.17 Signal transduction pathways by the Ras/MAP kinase cascade as well as via protein kinase C and subsequent activation of the nuclear transcription factor NFKB. The student is referred to earlier figures (7.6, 7.7, 7.8) giving some details of the specific pathways. Inhibitory actions of drugs and natural products are noted by the numbers within circles adjacent to the reaction and its product. (1) Growth factor-receptor inhibition; (2) inhibition of protein kinases; (3) inhibition of prenylation of G proteins. (Modified from Hinterding et al., 1998, with permission of the authors and publisher.)

Figure 20.17 Signal transduction pathways by the Ras/MAP kinase cascade as well as via protein kinase C and subsequent activation of the nuclear transcription factor NFKB. The student is referred to earlier figures (7.6, 7.7, 7.8) giving some details of the specific pathways. Inhibitory actions of drugs and natural products are noted by the numbers within circles adjacent to the reaction and its product. (1) Growth factor-receptor inhibition; (2) inhibition of protein kinases; (3) inhibition of prenylation of G proteins. (Modified from Hinterding et al., 1998, with permission of the authors and publisher.)

relatively selective for the epidermal growth factor receptor such as DAPH-1 (cf. Patrick and Heimbrook, 1996). Inhibitors of the protein kinase C family of serine/threonine protein kinases have involved both the use of active-site-directed inhibitors targeting both peptide substrate and nucleotide binding sites. However, cell-penetration problems remain as important factors in the use of these agents. Nucleotide binding-site-directed inhibitors include H-7 and staurosporine, while R0 32-0432 is an ATP-competitive inhibitor of some members of the protein kinase C family (cf. Patrick and Heimbrook, 1996). Inhibitors of the raf serine/threonine protein kinase and the mitogen activated kinases (MEK, MAP) have also been described affecting several mem-

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