10. Ras Dependent Signaling Pathways Flashcards
reverse transcriptase
synthesizes DNA from RNA
mechanism of a retrovirus
retrovirus
RNA virus whose genome consists of 2 identical copies of RNA that are base paired to tRNA
contain reverse transcriptase that allows the single-stranded RNA viral genome to be synthesized into a DNA strand that is complementary to the viral DNA
what does integrase do?
facilitates the integration of the double-stranded viral DNA into the nucleus & host genome
3 genes in a retrovirus?
gag
pol
env
what do LTRs do?
LTR=long terminal repeat
facilitate the integration of the viral chromosome into the hose DNA; contain promoters that drive viral gene expression
what do src encode?
tyrosine kinase
what is src (tyrosine kinase)’s role?
cell division
cell-cell interactions
intracellular comunication
c-src gene
native proto-oncogene
will cause cancer if mutated
v-src gene
oncogene located in a retrovirus
defective viruses need?
helper virus
what do helper viruses do?
they provide gag, pol, and/or env to allow the defective virus to replicate
monomeric G proteins are equivalent to?
the alpha subunit of trimeric G proteins
monomeric G protein function?
have GTPase activity
involved in cell signaling & growth
what accounts for 30% of all cancers?
activating mutations of c-ras
c-ras signaling involves (3 things)
- GTP-binding proteins with high affinity
- slow GTPase activity
- slow GDP dissociation
ras-GDP =
inactive
ras-GTP=
active
how do monomeric & trimeric G protein differ?
monomeric: GTPase slower to activate & slower to inactivate
what do monomeric & trimeric G protein have in common?
slow rate of GDP dissociation
ras is regulated by what 2 accessory proteins?
GAP & GEF
GTPase Activating Protein (GAP) function?
turns off ras
by accelerating intrinsic GTPase activity of c-ras
by activating GTPase, you inhibit ras via GTP hydrolysis
guanine nucleotide exchange factor (GEF) is also called..
guanine nucleotide releasing protein (GNRP) or guanine nucleotide exchange protein (GNEP)
what does GEF do?
activate ras
by accelerating GDP dissociation from c-ras
(activates by stimulating the rate-limiting step of GDP dissociation, turning ras on)
ras is also regulated by?
guanine nucleotide dissociation inhibitors (GDI)
what do GDIs do?
stabilize the c-ras GDP state
prevents rate-limiting step of GDP dissociation from occurring, ensuring ras is off
ras is stimulated by?
- inhibition of GAP
- activation of GEF
- inhibition of GDI
what is rho?
subfamily of the ras superfamily of GTPases
what is Rho’s function?
involved in cytoskeleton organization through serine-threonine protein kinases
rho’s relationship w/GEF & GAP & GDI?
GEF: stimulates GDP dissociation (activating)
GAP: turns Rho off
GDI: stabilizes inactive Rho
what does the MAP kinase cascade do?
activates a mitogen
what does a mitogen do?
simulate growth & cell division
MAP kinase cascade
map kinase-kinase-kinase-kinase --> map kinase-kinase-kinase --> map kinase-kinase --> map kinase --> enter nucleus, phosphorylate transcription factors
Raf
effector molecule of Map-kinase cascade
scaffold proteins
hold together proteins in the cytoplasm that function as binding sites for all components of a MAP kinase cascade
serve as regulators, help maintain selectivity
what does MAP kinase do when ras is activated
MAP kinase dissociates from the scaffold, enters the nucleus, activates a small set of TFs that regulate an activity
what is the function of immediate early genes
function as primary response genes: induce transcription within minutes of stimulation turn on independent protein synthesis shutoff dependent protein synthesis short mRNA half life (5-15mins)
what do protein products of immediate early genes do? (2 things)
- bind late response genes to turn them on
OR - bind genes or mRNA of the immediate early genes to turn them off or degrade them
characteristics of late response genes?
gene expression occurs after several hours
turn on dependent on protein synthesis
what happens in the presence of inhibitors or protein synthesis?
early-response genes are not turned off and delayed-response genes are not turned on because there are NO protein product of the early response genes produced (which bind late response genes to turn on)
