Growth factor receptor kinases

Hanai, N., Dohi, T., Nores, G. A., and Hakomori, S. (1988). A novel ganglioside, de-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth. /. Biol. Chem. 263, 6296-6301. 

Park OK, Schaefer TS, Nathans D. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Proc Natl Acad Sci USA 1996 93 13704-13708. 

Kwak EL, Jankowski J, Thayer SP et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006 12 4283 287. 

Stamos, J., Sliwkowski, M. X., Eigenbrot, C. (2002) Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 277(48), 46265-46272. 

Considerable cross-talk also occurs between different hormones at the level of receptor function. For instance, the diacylglycerol-activated protein kinase C phosphory-lates and thereby inhibits the activity of insulin and epidermal growth factor receptor kinases (epidermal growth factor is discussed in a later section). Likewise, when cAMP-dependent protein kinases are active they can inhibit receptors for epinephrine by phosphorylating them. 

Cohen, S., Ushiro, H., Stoscheck, C., and Chinkers, M. (1982). A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles./. Biol. Chem. 257, 1523-1531. 

Korutla, L. and Kumar, R., Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells, Biochim. Biophys. Acta, 1224, 597, 1994. 

Examples of compounds in various stages of clinical development include HER2 kinase inhibitors (ZD-1839 [158], CP-358774 [159] and PD-0183805 [160)], Bcr-Abl (CGP-57148, 161) and vascular endothelial growth factor receptor kinase inhibitors (SU-5416, 162). Although many of the starting leads were obtained by random screening approaches, further medicinal chemistry was aided by the availability of a number of crystal structures and other modelling approaches. 

Min mice have a truncating mutation in the murine APC gene at a position similar to that found in many FAP patients and develop multiple intestinal adenomas [24]. Heterozygous APC mice were therefore used to evaluate the efficacy of potential chemopreventative compounds on development of intestinal polyps [25]. The compounds tested were sulindac, a non-steroidal anti-inflammatory drag with estabUshed chemopreventative activity, and EKB-569, an irreversible inhibitor of the epidermal growth factor receptor kinase. 

Psammaplysilla purea. Shows moderate inhibitory activity against epidermal growth factor receptor kinase. Oil (as trifluoroacetate). [aj +24 (c, 0.98 in MeOH) (trifluoroacetate). 

Tu Y, Li F, Wu C (1998) Nck-2, a novel Src homology2/3-con-taining adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways. Mol Biol Cell 9 3367-3382... 

Song, W., Vacca, M. F., Welti, R., and Rintoul, D. A., 1991, Effects of gangliosides and de-N-acetyl G 3 on epidermal growth factor receptor kinase activity and cell growth, J. Biol. Chem. 266 10174-10181. 

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