Lecture 5 Flashcards
What is Ras? why is it seen in many cancers
Small GTPases that act as molecular switches by coupling cell membrane growth factor receptors to intracellular signalling pathways that regulate various cellular processes, monomeric, bind and hydrolyze guanine nucleotides. Seen in so many cancers because it is essential in signal transduction
how do Ras, HER2 and C-myc induce cancer
Ras: mutation
HER2-amplification
C-myc: translocation
what is EGFR
tyrosine kinase.
What is a tyrosine kinase
an enzyme that can transfer a phosphate group from ATP to a protein in a cell. On/off switch in many cellular functions
T/F phosphorylation is reversible
True
how does a proto-oncogene become and oncogene
Mutation
amplification
Gene translocation
What is EGF?
Hormones bind to EGF which cause dimerization of EGF monomers, which begins the activation cascade of the Ras protein
Describe Ras protein activation
Hormones bind to EGF monomers which cause dimerization, and phosphorylation of receptor tyrosine residues
GRB2 and Sos couples receptor to inactive Ras
GDP dissociates from Ras, GTP binds and active Ras dissociates from Sos
What’s the function of Sos in the third step of Ras activation
Promotes dissociation of GDP
What do GAP and GEF do?
GAP: Inactivates Ras
GEF: activates Ras
which codon mutations are the most common in cancer?
12
What mutation is responsible for H-ras oncogene activation?
V12, single base-pair mutation, glycine to valine, impairs GTPase activity
What is Ras binding to when it is active? inactive?
Active: GTP
inactive: GDP
why does the Ras protein activation/inactivation cycle run in one direction?
Hydrolysis of GTP to GDP is irreversible
which cancer is the most common to see a point-mutate ras gene
pancreatic cancer, 90% of pancreatic cancers have point mutated ras gene