Negative regulation of ErbB family receptor tyrosine kinases.
Receptors of the EGF receptor or ErbB family of growth factor receptor tyrosine kinases are frequently overexpressed in a variety of solid tumours, and the aberrant activation of their tyrosine kinase activities is thought to contribute to tumour growth and progression. Much effort has been put into developing inhibitors of ErbB receptors, and both antibody and small-molecule approaches have exhibited clinical success. Recently, a number of endogenous negative regulatory proteins have been identified that suppress the signalling activity of ErbB receptors in cells. These include intracellular RING finger E3 ubiquitin ligases such as cbl and Nrdp1 that mediate ErbB receptor degradation, and may include a wide variety of secreted and transmembrane proteins that suppress receptor activation by growth factor ligands. It will be of interest to determine the extent to which tumour cells suppress these pathways to promote their progression, and whether restoration of endogenous receptor-negative regulatory pathways may be exploited for therapeutic benefit.
Sweeney
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UC Davis Cancer Center, University of California, Research Building III, Room 1400, 4645 2nd Avenue, Davis, Sacramento CA 95817, USA. casweeney@ucdavis.edu
Carraway
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KL
D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018815:Genes, erbB / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D050722:Oncogene Protein v-cbl; D011506:Proteins / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases
D050722:Oncogene Protein v-cbl; D011506:Proteins; D015682:Retroviridae Proteins, Oncogenic; C452580:RNF41 protein, human; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases