Term
| Where do cells recieve signals form the environment beyond the plasma membrane |
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Definition
| antigens, hormones, nuerotransmitters, touch |
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Term
| Features of Signal-Transducing Systems |
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Definition
1. Specificity
2. amplification
3. desensitization/adaption ( receptor activation triggers a feedback that shut off the receptor or removes it from the cell)
4. integration (2 opposite charges) |
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Term
where do the link up with
g-protien
enzyme
ligan-gated ion channels
other membrance recptors
nuclear receptors
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Definition
epinephrine (receptor)
insulin
lnicotinic acetylcholine
integrin
sterile |
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Term
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Definition
A membrane-bound or soluble protein or protein
complex, which exerts a physiological effect (intrinsic effect),
after binding its natural ligand. |
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Term
| Six General Types of Signal Transducers |
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Definition
G-protein-coupled receptor
receptor tyrosine kinase
receptor guanylyl cyclase
adhesion receptos (integrin)
Gated ion channel
nuclear recptor |
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Term
| G-protein-coupled receptor |
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Definition
external ligand (S) binding to receptor (R) activate an intracellular GTP-binding protein (G), which regulates an enzyme (ENZ) that generates an intracellular second messanger, X
50% of all drugs on the market target GPCR |
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Term
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Definition
| ligand binding activates tyrosine kinase activity by autophosphorylation |
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Term
| Receptor guanylyl cyclase |
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Definition
| ligand binding to extracellular domain stimulates formation of second messanger cAMP |
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Term
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Definition
| binds molecules in extracellular matrix, changes conformation, thus altering its interaction with cytoskeleton |
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Term
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Definition
| opens or closes in response to concentration of signal ligand or membrane potential |
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Term
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Definition
| steriod binding allows the receptor to regulate the expression of specific genes |
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Term
G-protein coupled receptor
-beta-adrenergic receptor which mediates the effect of epinephrine is the target of ________
-beta-adrenergic receptor acts through the second messanger____ |
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Definition
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Term
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Definition
beta blocker, for hypertension (HT), antagonist of epinenphrine cascade.
off labeled kinds: tremors, stage fright |
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Term
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Definition
| beta agonist, low blood pressure, from shock, heart attack, asthma attack (beta 2) |
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Term
| three essential components of G-protein coupled receptors (GPCP) |
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Definition
-Plasma membrane receptor with seven
transmembrane helical segments
–Effector enzyme in the plasma membrane that
generates an intracellular 2nd messenger
–Guanosine nucleotide binding protein (G protein)
that activates the effector enzyme |
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Term
| beta adregenic pathway (7 steps) |
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Definition
1. epinephrine binds to specific receptor
2. occupied receptor cause replacement of the GDP bound to G(s) by GTP, activates G(s)
3. G(s) (alpha subunit) moves to adrenayl cyclase and activates it
4. adrenayl cyclase catalyzes formation of cAMP
(can go to ways)
first is: 5.cAMP activates PKA
6. phosphorylation of cellular protein by PKA causes cellular response to epinenphrine
second way: 7. cAMP is degraded, reversed activation of PKA
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Term
| Some signals that use cAMP as second messenger |
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Definition
| Glucagon, histamine, serotonin, somatostatin |
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Term
Enzyme-linked Membrane Receptors
Many membrane receptors consists of _____ and of____
-The most common catalytic domains have
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Definition
extracellular binding domain and of intracellular catalytic domain
-tyrosine kinase activity (add phosphate group to itself; auto-phosphorylation) |
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Term
Epidermal growth factor receptor (EGFR)
Cell surface receptor for members of the ___ family of extracellular ______ |
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Definition
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Term
Epidermal Growth Factor Receptor (EGFR)
-Mutations affecting EGFR expression or activity may result in ______ |
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Definition
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Term
Epidermal Growth Factor Receptor (EGFR)
1. Exists in its ______
2. activated by binding of its _____ (two big ones are EGF and TGF alpha)
3. transition to ______ |
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Definition
1. inactive monomers
2. specific ligand
3. active form (homodiner) |
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Term
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Definition
Tyrosine kinase inhibitors Colorectal cancer, non small cell lung cancer, squamous cell carcinoma of head and neck
Monoclonal |
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Term
Monoclonal Antibodies
bind to the EC of EGFR, _______
Cetuximab
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Definition
prevents ligand binding
iv injection
colorectal, head and neck cancers
30,000 for 8 weeks
combination therapy with chemotherapy |
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Term
Tyrosine Kinase Inhibitors
bind to IC domain of EGFR, _______
Gefitinib (Iressa)
selective inhibitor of EGFR tyrosine kinase domain, binds to the _______ |
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Definition
prevents phosphorylation
ATP binding spot
advanced or metastic non small lung cancer
infrequent side affects
may be replaced by erlotinib (efficacy)
$1575 per 21 day supply (average of 5 months of treatment)
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Term
Nuclear receptor
-tamoxifan |
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Definition
steriod hormones
act in the nucleus to alter gene expression
-used for estrogen dependent breast cancer
cell division depends on presence of estrogen
tamoxifan is an antagonist |
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Term
| Avenues for COmbination Therapy |
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Definition
-Dual Inhibition of EGFR Signaling Using the
Combination of Cetuximab and Erlotinib
• Clinical trial started October 2008
–Cetuximab 400mg/2X per week
–Erlotinib 100mg daily
used for when all other treatments have failed (life expectancy is 6 months) |
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Term
| other tryosine kinase inhibitors (dasatinib) |
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Definition
Dasatinib:
for luekemia
oral
downside are the side effects (nausea,stomach, fever, etc). Not bad side effects just a lot of them
lots of drug interaction |
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Term
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Definition
takes 24 hours
interphase: G1, sythensis (S), G2
cell division: Mitosis (M) |
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Term
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Definition
grow fast
best target is in M phase
if bad cell hits a good cell, then good cell dies |
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