A mechanism of c-raf-1 activation: fusion of the lipocortin II amino-terminal sequence with the c-raf-1 kinase domain.

In order to understand the mechanism of oncogenic activation, we have analyzed the c-raf-1 gene from the GL-5-JCK human glioblastoma, which underwent rearrangement during transfection experiments. Nucleotide sequencing of cDNA clones derived from the 2.5 kb raf-mRNA, which is a major transcript of raf in NIH3T3 cells transformed with GL-5-JCK DNA, revealed that this mRNA contains sequences derived from the human c-raf-1 gene and the human lipocortin II gene. Translation of the 2.5 kb raf-mRNA predicted a fusion protein consisting of 16 amino-terminal amino acid residues of the lipocortin II and 370 carboxy-terminal amino acid residues of the c-raf-1 protein which contains the kinase domain. Expression of the lipocortin II-raf cDNA using the murine sarcoma virus long terminal repeat as promoter resulted in the transformation of NIH3T3 cells.