Oncogene activation: c-raf-1 gene mutations in experimental and naturally occurring tumors

摘要: Abstract We demonstrate here consistent point mutations of the c-raf-1 proto-oncogene, within a small region kinase domain, in mouse model for chemical tumor induction. This is first demonstration mutated raf genes vivo, and isolation activating vivo domain proto-oncogene. The specific where these are clustered also has biological significance. precisely 5 independently generated monoclonal antibodies raised against Raf-1 map to [29], predictions based upon crystal structure A identify this as substrate pocket. tumors examined show selective specificity that another family genes, ras proto-oncogenes which frequently activated by mutation both animal human [15-21,26], not involved. Our finding consequences further evaluation role development, it emphasizes need examine at sequence level. In fact preliminary screening lung indicates amino acid 533 (John Lyons, personal communication). Finally, cumulative data on critical signal transduction occurrence oncogenic [32–41] highlight enzyme an attractive target development novel anticancer regimens.