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definition of signal transduction
one type of signal is converted into another one
categories of signal transduction
paracine
endocrine
neuronal
autocrine
paracine
goes a short distance and effects multiple cells in vicinity
ex. pacemaker cell
endocrine
travels over larger distances, travels in bloodstream to target cell
ex. hormones
neuronal
hybrid type
stimulates neuron that causes release of neurotransmitter over a short space called the synapse
autocrine
cell “self-targets” signal, will go back to cell it was released from
extracellular cells act rapidly when
altering an existing protein
ex. contracting muscles
extracellular signals act slowly when
you have to make a new protein (proteins synthesis)
size and type of protein can dictate how long it takes
ex. building muscle
cell surface receptors use
cell surface receptor proteins that sends message to intracellular signaling molecule
cell surface receptor signals can’t
cross the membrane
intracellular receptors receive
small hydrophobic signal molecules that are able to cross the membrane to the intracellular receptor (ex. hormones)
major types of cell surface receptors
ion channel-coupled receptors
G-protein coupled receptors (GPCR)
enzyme-coupled receptors
ion channel-coupled receptors
signal molecule attaches to channel to open channel and let selected ions through
once ions pass into cytosol, they can become 2nd messengers
G-protein coupled receptors (GPCR)
once receptor receives signal, it recruits and activates G protein
G protein recruits and activates the enzyme (which can be a 2nd messenger)
enzyme-coupled receptors
signal molecules bind to 2 receptors at the same time that have enzyme activity (enzyme built in)
2nd messengers help
amplify and spread the intracellular signal
common 2nd messengers
cyclic AMP (most common)
cyclic GMP
inositol triphosphate
Diacylglycerol (DAG)
calcium
two common 2nd messenger systems
phosphorylation & G-protein
protein phosphorylation
kinase cascade
scaffold helps bring kinases closer together so they can phosphorylate
protein kinase means
on
protein phosphatase means
off (removes phosphate)
with G-protein, GTP binding means
on
with G-protein, GDP hydrolysis means
off (breakdown of GTP to GDP)
stages of cell cycle
G1 phase
S phase
G2 phase
M phase
G1 and G2 phase
growth
S phase
synthesis/duplicate DNA
M phase
mitosis/cell divides
interphase is considered
G1, S, and G2 phase
CDKs
cyclin dependent kinases
CDK only work when
kinases are bonded to cyclin protein
in order to get through a CDK
you must have the right amount of cyclin to turn on kinase
degrading cyclin
turns off
S-CDK (S cyclin)
between G1 and S
M CDK (M cyclin)
between G2 and M
G1/S checkpoint
checks to make sure no DNA is damaged
G2/M checkpoint
checks to make sure complete replication of DNA has occurred and no new mutations
cancer has occurred in
man and other animals throughout recorded history
“karkinos” (Hippocrates) means
crabs
cancer can arise because of
genomic instability (damage to DNA)
examples of genomic instability
radiation
chemicals
loss of repair mechanisms
some viruses
to create a cancer cell you need
a series of mutations
alterations in multiple pathways are needed to
transform a normal cell to cancer cell
what alterations are needed to transform a normal cell to cancer cell
cell proliferation
DNA damage response
cell growth
cancer cells have mutations that turn on BLANK and BLANK signaling pathways all of the time
survival and growth
cancer cells disable BLANK, which causes the cell to grow out of control
death signaling pathways (apoptosis)
proto-oncogene is the
normal form of the gene
oncogene is the
mutation form, which is a dominant mutation that causes excessive cell survival, proliferation, or both
Ras gene (proto-oncogene)
mutation in this gene causes the Ras protein to always be active, promoting cell proliferation
tumor repressor gene is the
normal gene
for mutations in tumor suppressor genes
both copies must be mutated (recessive)
Retinoblastoma (Rb) controls the activity of
E2F transcription factors
E2F factors are needed for
S-phase genes
active G1 CDKs phosphorylate Rb which will
inactive it while it attaches to the E2F protein, causing it to release the E2F protein, allowing S-phase to progress
BLANK or BLANK can inactive Rb
mutations or viral proteins (ex. human papillomavirus)
Rb mutation can lead to
eye tumors in young children
inactivation of both copies of p53 allows
cancer cells to continue to survive and divide, even in the presence of damaged DNA
apoptosis =
programmed cell death
cell have apoptosis to
make sure cells with abnormal DNA, cell cycle division, or other messed up critical pathways are killed to protect the organism
genome alteration in proto-oncogene
mutation in coding sequence
gene amplification
chromosome rearrangement
mutation in coding sequence of proto-ocnogene normal result
hyperactive protein made in normal amounts
gene amplification in proto-ocnogene normal result
normal protein overproduced
Chromosome rearrangement in proto-oncogene normal result
nearby regulatory DNA sequence causes normal protein to be overproduced
Chromosome rearrangement in proto-oncogene abnormal result
fusion to actively transcribe gene produces hyperactive fusion protein
tyrosine kinase receptor is a type of
hyperactive receptor fusion that can lead to cancer
BLANK, BLANK, BLANK can lead to cancer hyperactive receptor that is ON ALL THE TIME
point mutation
fusion of receptor intracellular domain with 2nd messenger
overproduction of receptor
PDGF acts through
receptor tyrosine kinase (IDK)
TEL-PDGFR-beta is an example of
oncogene-fusion
the helix-lopp-helix domain of TEL transcription factor fused to BLANK causing dimerized receptor
PDGF receptor beta
the TEL-PDGFR-beta causes
chronic Myelomonocytic Leukemia (CMML) (white blood cell cancer)
first parentheses in translocation gives
chromosomes involved
second parentheses gives
precise location
q =
long arm
p =
short arm