What makes v-erbB a dominant oncogene?
It is only the C terminus of the EGF receptor so has no growth factor binding domain and is thus constitutively active
What makes PDGF a dominant oncogene?
If a cell is infected with an RNA tumor virus, PDGF is expressed INSIDE the cell and this autocrine signaling can lead to cancer
What makes v-fos and v-jun dominant oncogenes?
If cell is infected with RNA tumor virus, the transcription factors v-fos and v-jun are expressed and transcribe genes that can lead to cancer
Are there dominant oncogenes in the Ras pathway?
Yes: ligand itself, receptor, Ras, Raf, transcription factors
Normal pathway leading to Ras signaling
Growth factor ligand binds to receptor → receptor is phosphorylated → now Grb2, which is attached to GNEF via SH3 domains, recognizes and binds phosphorylated receptors → Ras binds GNEF → binding causes Ras to release GDP and take up GTP → Ras-GTP is now active and can signal → GAP binds Ras to help it cleave GTP to GDP and Ras is now inactive
What does active Ras (Ras-GTP) do?
Activates a protein kinase cascade:
Ras → RAF → MAPKK → MAPK → nucleus to phosphorylate transcription factors, making them active
What is the difference between viral Ras and cellular Ras?
Viral Ras cannot interact with GAP, so it is locked in the "ON" position
Can single point mutations in genes contribute to cancer?
1) Ras unable to bind GAP
2) G alpha subunit leads to endocrine tumors
3) bRaf mutation in 2/3 of melanoma tumors (furthermore, 50% of patients have exact same mutation)
Is Ras mutated in many human cancers?
Yes, 1/3 of human cancers have Ras mutation
Diagram all the steps of the Ras pathway. From initation to gene expression.