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42 Cards in this Set

  • Front
  • Back
Tertiary structure of Ha-ras has a ______ domain
CAAX
RAS has a molecular weight of ____ is ______ in shape and contains (4 secondary structures)
21K; globular; alpha helices, beta ribbons, loop, and turn regions
Most human tumors have ___ mutations
ras
GTP binding site on the RAS protein located along one face of the protein on a region where oncogenic mutations are observed at which two codons?
61 and 12
Codons 61 and 12 are ____ regions.
turn
The GTPase activating protein (GAP) binds RAS at _____
the large AA loop extending from GTP binding site
In the ____ form RAS binds GTP, in the ______ form RAS binds GDP.
active; inactive
RAS inhibitors should have _____ activity
anti-tumor
RAS is located on which surface of the plasma membrane
inner
RAS responds to signals from the outside by exchanging ____ for _____
GTP for GDP
The exchange of GTP for GDP si stimulated by ____ protein
SOS protein
SOS protein is activated by
GRB2
GRB2 is activated by
receptor kinase
When RAS is bound by _____ it activates a downstream ______ cascade that activates transcription factors and genes for growth
GTP; kinase
RAS-GTP activity is turned off by intrinsic ______ activity of RAS in concert with extrinsic GAP
GTPase
The RAS-GDP structure is inactive in
signal transduction and promotion of cell division
The signal transduction pathway begins with
growth factor binding to a surface receptor
RAS mutations in codons 12 and 61 short circuit the signal transduction pathway by
introducing structural changes which inhibit GTPase
When RAS inhibits GTPase this keeps the protein in which form
GTP-bound form
RAS protein must be targeted where to function properly in signal transduction
inner surface of plasma membrane
Human carcinomas contain mutations with
RAS protein
Drugs to inhibit RAS protein targeting should inhibit
growth of tumors with RAS mutations (duh)
RAS is targeted to the cell membrane by a fancy enzyme
farnesyl transferase
Farnesyl transferase adds a farnesyl group to
Cysteine on the C terminal CAAX domain of RAS
RAS is anchored to the plasma membrane by
farnesyl lipid group
This amino acid is targeted the farnesyl group
cysteine on CAAX domain of RAS
The tetrapeptide CAAX inhibits which enzyme in vitro
farnesyl transferase
What keeps CAAX from inhibiting farnesyl transferase in vivo because
it is charged and polar, therefore cannot diffuse through the cell membrane
Hydrophobic benzodiazepine molecule mimics
the AA dipeptide turn on CAAX motif
For a CAAX domain to diffuse into a cell it must have the attachment of (2 things) where it can inhibit RAS
an N terminal Cysteine and C-terminal AA
Benzodiazepine is a structural relative to
Valium (yes, please)
BZA-5B contains an N-terminal _____ and a _____ at the C-terminus
Cysteine methyl amine; carboxymethyl methionine
BZA-5B inhibits ______ but not ______
mutant RAS transformed cells; SRC transformed cells
RAS mutant transformed cells have
Specificity
These code for transcription factors that regulate genes whose products are necessary for cell division and growth
Nuclear proto-oncogenes
Signal transduction from a cell-surface event involves
phosphorylation cascades
Phosphorylation cascades result in
stimulation in transcription factor activity and transcription of growth related genes
Production of transcription factors ___ and ____ is required for cell division
FOS; JUN
FOS and JUN factors form a heterodimer termed
AP-1
AP-1 functions in
transcription and activation of growth related genes
In the _____ form RAS binds GTP
active
In the _____ form RAS binds GDP
inactive