geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling


, : The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. Journal of Biological Chemistry 272(5): 2927-2935

Deregulation of signaling by the epidermal growth factor receptor (EGFR) is common in human malignancy progression. One mutant EGFR (variously named DELTA-EGFR, de2-7 EGFR, or EGFRvIII), which occurs frequently in human cancers, lacks a portion of the extracellular ligand-binding domain due to genomic deletions that eliminate exons 2 to 7 and confers a dramatic enhancement of brain tumor cell tumorigenicity in vivo. In order to dissect the molecular mechanisms of this activity, we analyzed location, autophosphorylation, and attenuation of the mutant receptors. The mutant receptors were expressed on the cell surface and constitutively autophosphorylated at a significantly decreased level compared with wild-type EGFR activated by ligand treatment. Unlike wild-type EGFR, the constitutively active DELTA-EGFR were not down-regulated, suggesting that the altered conformation of the mutant did not result in exposure of receptor sequence motifs required for endocytosis and lysosomal sorting. Mutational analysis showed that the enhanced tumorigenicity was dependent on intrinsic tyrosine kinase activity and was mediated through the carboxyl terminus. In contrast with wild-type receptor, mutation of any major tyrosine autophosphorylation site abolished these activities suggesting that the biological functions of DELTA-EGFR are due to low constitutive activation with mitogenic effects amplified by failure to attenuate signaling by receptor down-regulation.

US$19.90

PMID: 9006938

DOI: 10.1074/jbc.272.5.2927


Other references

Matschke R.G.; Plath P., 1984: Early diagnosis of hearing impairment a simple method for mass screening neo nates. Archives of Oto-Rhino-Laryngology 239(2): 121

Bousser, J.; Christol, D.; Buoillier, J.M., 1957: Thrombocytopenic purpura in a diabetic treated with sulfonylurea BZ 55. Bulletins et Memoires de la Societe Medicale des Hopitaux de Paris 73(27-28): 943-948

Slaff, M., 1981: Observations on the effort to control insect-borne diseases in Panama. Proceedings of the annual meeting New Jersey Mosquito Control Association: 8th) 43-46

Bianchi, C.; Bianchi, T.; Grandi, G., 2006: Malignant mesothelioma of the pleura among seafarers. A large amount of data indicates that seafarers are at risk for asbestos disease. To trace the outlines of pleural mesothelioma among seafarers. Pleural mesotheliomas diagnosed among seamen in the Trieste-Monfalcone area, Italy, in the period 1973...

Tatevossian, A., 1985: Some factors affecting the diffusion of [14C]-lactate in human dental plaque. The apparent diffusion rate, D, of lactate was significantly retarded in dental plaque fluid and a simulated plaque fluid consisting of a chemically-defined solution of salts, amino acids and albumin in phosphate buffer at pH 6.5. Metabolic utiliz...

La-Perna, R.; Ragaini, L., 2008: Dyolia N gen from the European Miocene-Pleistocene Protobranchia Nuculanidae. The nuculanids Leda mendax Meneghini in Appelius, 1871, from the Plio-Pleistocene of Italy and Leda reussi Hornes, 1865, from the Middle Miocene of Austria, are almost equilateral in shape, not rostrate, with a very shallow pallial sinus and a po...

Manghnani Murli H.; Webb Sharon L., 1986: Elasticity of CoO as a function of pressure and temperature; comparison with transition metal oxides. Papers and Proceedings of the General Meeting - International Mineralogical Association Pages 165-166

Nielsen, N.-Rod; Strandberg-Larsen, K.; Gronbaek, M.; Kristensen, T., S.; Schnohr, P.; Zhang, Z.-Feng, 2007: Self-reported stress and risk of enclornetrial cancer: A prospective cohort study. Objectives: To assess a possible relationship between perceived stress and first-time incidence of primary endometrial cancer. Psychological stress may affect the synthesis and metabolism of estrogens and thereby be related to risk of endometrial...

Shyti, H., 1964: Results Of Combined Hormonal And Antibacterial Therapy Of Serofibrinous Exudates. Shendetesia Popullore 19: 25-32

Strom Richard N., 1996: Influence of aquitards on the hydrogeochemistry of an Atlantic Coastal Plain aquifer. Abstracts with Programs - Geological Society of America 28(7): 24