Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor.
Our recent studies with cell mutants indicate that a cascade shared by the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) signals exists in NRK cells and mediates oncogenic signals induced by many oncogenes (A. Masuda, S. Kizaka-Kondoh, H. Miwatani, Y. Terada, H. Nojima, and H. Okayama, New Biol. 4:489-503, 1992). We have employed the antisense RNA technique to investigate possible involvement of Raf-1 kinase in this signal transduction cascade. NRK cell clones highly reduced in the Raf-1 production are generated by the expression of a c-raf-1 antisense RNA. They have no apparent growth defects and retain proper mitotic responses to growth factors but are refractory to transformation by EGF or PDGF plus transforming growth factor beta, v-erbB, v-fms, v-K-ras, v-mos, v-fos, v-src, simian virus 40 large T, and polyomavirus middle T but not by v-raf or adenovirus E1A. These results not only support our model for the oncogenic signal cascade but also lead to the conclusion that Raf-1 protein kinase is a downstream component of this oncogenic signal cascade shared by EGF and PDGF.
Kizaka-Kondoh
S
S
Department of Molecular Genetics, Osaka University, Japan.
Sato
K
K
Tamura
K
K
Nojima
H
H
Okayama
H
H
D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000378:metabolism*; D009857:Oncogenes; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf