Block 3 Lecture 5 -- Growth Factors and Oncogenes Flashcards
What mechanisms activate proto-oncogenes to oncogenes?
1) point mutations/deletions in coding sequences
2) point mutations/deletion is regulatory sequences
3) chromosomal translocation
4) insertional mutagenesis
5) gene amplification
What results from a point mutation/deletion in a coding sequence?
structural and functional changes
What results from a point mutation/deletion in a regulatory sequence?
over-expression of protein
What results from a chromosomal translocation?
fusion proteins with novel function
What results from insertional mutagenesis?
aberrant protein expression
Describe the structure of EGFR.
receptor TK
3 domains
– extracellular, transmembrane, cytoplasmic
– not all respond to extracellular ligand
– not all have cytoplasmic tail
How is intracellular signaling initiated from EGFR?
1) receptors dimerize
2) autophosphorylation
3) multiple signaling cascades
What are the 2 main signaling cascades from EGFR?
Ras/Map Kinase
Src/Stat
What is Ras?
a GTPase inactivated in the GDP-bound state
How is Ras a major oncogene?
mutations causing decreased hydrolysis increases Ras activity
What is Src?
a kinase inactivated in its phosphorylated form
What are Src’s domains?
1) kinase
2) Tyr
3) Sh3
4) Sh2
How does phosphorylation of Src inactivate it?
Tyr-PO4 folds up to bind SH2, blocks kinase domain
What is BCR-ABL?
a fusion protein from Philadelphia chromosome
What are the domains of Abl?
1) kinase
2) DNA-binding
3) actin-binding
4) Sh2
5) Sh3
