Mutational activation

Sequential mutations within colonic epithelium result in cellular replication or enhanced invasiveness. Genetic changes include mutational activation of oncogenes and inactivation of tumor suppressor genes. 

Landis, C.A., Masters, S.B., Spada, A., Pace, A.M., Bourne, H.R. and Vallar, L. GTPase inhibiting mutations activate the a chain of Gj and stimulate adenylyl cyclase in human pituitary tumours (1989) Nature 340, 292-696... 

Amacher, D.E. Turner, GN. (1985) Tests for gene mutational activity in the L5178Y/TK assay system. Prog. Mutat. Res., 5, 487 96... 

Thus, mutational activation of EGFR and K-Ras within the same tumor cell may result in senescence when pl6 or ARF activities have not been lost. Alternatively, EGFR and K-Ras mutations within the same tumor cell may trigger a strong apoptotic response... 

Ras genes are frequently mutated in chemically induced animal tumors and are the most frequently detected mutated oncogenes in human tumors. Approximately 20-30% of all human tumors contain mutated ras. The Ras subfamily includes H-ras, K-ras, and N-ra.v, and all have been found to be mutationally activated in numerous types of tumors from a large variety of species including humans. 

Ekberg H, Swensson PJ, Simanaitis M, et al, Factor V R506Q mutation (activated protein C resistance) is additional risk factor for early renal graft loss associated with acute vascular rejection, Transplantation 2000 69(8) I 577-1 581. 

Flaherty KT et al (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363 809-819... 

C. A. Landis, S. B. Masters, A. Spada, A. M. Pace, H. R. Bourne, and L. Vallar. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature, 340 (6236), 692-696, 1989. 

Mutational activation, in addition to over-expression of the tyrosine kinase receptor, is now believed to be necessary to achieve full tumorigenic potential46. 

Padyana AK. Qiu H, RoU-Mecak A, Hinnebusch AG, Burley SK. 2005. Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2a protein kinase GCN2. J Biol Chem 280 29289-29299. 

Jeffers, M. et al.. The mutationally activated Met receptor mediates motility and metastasis, Proc. Natl. Acad. Sci. USA. 95,14417, 1998. 

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