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145 Cards in this Set
- Front
- Back
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what are two biogenic amines
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epinepherine
norepinephrine |
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what are the binding properties of receptors
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saturability
affinity specificity |
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what is Ka equal to
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1/Kd (association constant)
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is a specific binding curve able to be to show saturablilty
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yes
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is a non specific binding curve able to show saturabiliy
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no
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what is a scatcher plot
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enable us to plot binding ina linear form to get the total # of binding site/the dissassocition constant
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In a scatcher plot what corresponds to the Y and X intercepts
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Y=bound/free (hormones)
X=Bmax (R+RL) |
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what are 5 ways that signal transmission is accompilished
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gene activation
opening of ion channels by linked receptr enzymatic activity ligand-stimulated autophosporylation activation of a specific G protein |
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how does a gated ion channel work
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opens or closes in response to intracellular or extracellular signal ligand concentration or membrane potential
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what is an example of a receptor enzyme
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protein tyrosine kinase
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how does receptor enzymes work
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ligand binds to the extracellular domain and stimulates intracellular enzymatic activity
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what is the general process of how a serpentine receptor works
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ligand binds receptor
receptor activates intracellular GTP-binding protein (G) G regulates and enzyme that generates second messengers |
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what are 3 ways that desensitization is accomplished
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1. reduction in receptor #
2. localization of receptors at the cell sur 3. efficiency of the signal transmission generally all specific for agonists |
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what is adaptation
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the ability of signal systems to adjust to response to different levels of signals
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how does an agonist inhibit a signal response
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by blocking the binding of the agonist
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T or F receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface
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T
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T or F signal amplification is and aspect of signaling systems
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T
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what is integration (cross talk)
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signals can oppose each other or reinforce each other. this can take place at multiple steps
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what are four ways that ion channels are regulated
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ligand gated channels
voltage-gated channels mechanically gated channels covanlent modification |
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what causes cystic fibrosis
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the CL- channels have been mutated which affect the ability of them to be regulated by covalent modification
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what type of transport is involved in channels
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passive transport.
all the regulation of the channels disscussed work by passive diffusion down their electrochemical gradients |
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what ions does acetylcholine dependent gated protein allow
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Ca+, Na+ or K+
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in acetylcholine-dependent opening of gated proteins what happens when acetylcholine binds
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a rotation of bound alpha helices to place polar aspect in the interior of the protein to facilitate Ca+, Na+ or K+
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what is tertodotoxin
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a neuro toxin that targets ion channels from japanese puffer fish
targets voltage-gated Na+channels |
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what is saxitoxin
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a neuro toxin that targets ion channels
from red tide targets voltage-gated Na+ channels |
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what is Alpha-bungarotoxin
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a neuro toxin that targets ion channels
venom from a banded krait snake that inhibits the nicotinic acetylcholine receptor |
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dendrotoxin
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a neuro toxin that targets ion channels from mamba snakes that block neuronal voltage dependent K+ channels
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what do spider venom toxins inhibit
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calcium channels or sodium potassium channels
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what are conotoxins
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a neuro toxin that targets ion channels from cone snails, most selective of all inhibitors, can select for voltage sensitive sodium, calcium or potassium channels and ligand-gated channels
these are being studied as starting materials for new drugs |
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what are three channel specific drugs
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local anesthetics, anticonvulsants, and antiarrhythmics
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what is the most common type of enzyme activity found intrinsic to a transmembrane receptor
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Protein Tyrosine Kinase
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what types of signaling use PTK's
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growth factors
insulin cytokines (interferons and interleukins) |
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are receptors for PTK's single pass transmembrane proteins or multiple pass
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single pass with ligand binding domain in the extracellular surface
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what is unusual about the insulin receptor binding and protein tyrosine kinases domains
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once the insulin ligand binds two dimers (heterodimers) for a tetrameric complex via disulfide bonds
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what a kinase insert region
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an important site for autophosphorylation and protein-protein interacitons
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in receptor tyrosine kinases where are the aminoterminal and carboxytermial domains located
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aminoterminal=extracellular
carboxyterminal=intracellular |
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what type of site is created by autophosphorylation
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phosphotyrosine site for binding of the SH2 protein
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autophosphorylation can take place in two spots what are they
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cytoplamic domain (growth factors/insulin)
the PTK receptor (cytokine receptor) |
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what differs among effector proteins
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the differ in the the SH2 structure which effect which specific tyrosine phosphate sites it reacts with
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recruitment of effector proteins propogates the GF signal by which two ways
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1. facillatating the binding of the effector protein to the its binding partner
2. facilitating phosphorylation of tyrosine with its accompanied activation of PTK |
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what two hormones regulate cell proliferation
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insulin
growth factor |
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what is a Ras protein
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a monomeric guanyl nuclotide-binding protein (G-protein) that activate the MAP kinase cascade which changes gene expression
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in the major proliferative response involves what protein
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the ras protein
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what is SOS
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a guanine-nucleotide exchange factor for Ras (in ras this stimulate the exchange of GDP for GTP (active))
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between what two proteins does phosporylated tyrosine bind
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Grb2 and SH2
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what is the most common type of enzyme activity found intrinsic to a transmembrane receptor
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Protein Tyrosine Kinase
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what types of signaling use PTK's
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growth factors
insulin cytokines (interferons and interleukins) |
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are receptors for PTK's single pass transmembrane proteins or multiple pass
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single pass with ligand binding domain in the extracellular surface
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what is unusual about the insulin receptor binding and protein tyrosine kinases domains
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once the insulin ligand binds two dimers (heterodimers) for a tetrameric complex via disulfide bonds
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what a kinase insert region
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an important site for autophosphorylation and protein-protein interacitons
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in receptor tyrosine kinases where are the aminoterminal and carboxytermial domains located
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aminoterminal=extracellular
carboxyterminal=intracellular |
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what type of site is created by autophosphorylation
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phosphotyrosine site for binding of the SH2 protein
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autophosphorylation can take place in two spots what are they
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cytoplamic domain (growth factors/insulin)
the PTK receptor (cytokine receptor) |
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what differs among effector proteins
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the differ in the the SH2 structure which effect which specific tyrosine phosphate sites it reacts with
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recruitment of effector proteins propogates the GF signal by which two ways
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1. facillatating the binding of the effector protein to the its binding partner
2. facilitating phosphorylation of tyrosine with its accompanied activation of PTK |
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what two hormones regulate cell proliferation
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insulin
growth factor |
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what is a Ras protein
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a monomeric guanyl nuclotide-binding protein (G-protein) that activate the MAP kinase cascade which changes gene expression
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in the major proliferative response involves what protein
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the ras protein
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what is SOS
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a guanine-nucleotide exchange factor for Ras (in ras this stimulate the exchange of GDP for GTP (active))
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between what two proteins does phosporylated tyrosine bind
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Grb2 (and SH2 containing adaptor protein)
SOS |
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what does and activated Ras do
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it binds and activates Raf-1
Ser/Thr selective protein kinase |
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what does Raf-1 do
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it activates MEK
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what does MEK do
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it activates ERK
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what does ERK do
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it phosoporylates proteins such as important transcription factors like pp90(kinase that phosporylates S6)
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how is Ras's function in cancer patients
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highly mutated
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how is phosphatidylinositol 3-kinase activated
2 ways |
growth factor receptors
IRS-1 |
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what does PI3-K generate
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3,4,5 phosphatidylinositol PIP3 from PIP2
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what is a Plekstrin homology domain (PH domain0
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a region of protein that binds phosphoinositides and Beta/gamma units of G proteins as well protein kinase C
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where does PIP3 interact with proteins
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the PH domain
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what is attacked to the PIP3
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PKB protein kinase B
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what does PTEN do and one what molecule does it act
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terminates the signaling pathway
acts on PIP3 to change it back to PIP |
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what is central to insulins effects on metabolism
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PI3/PKB pathway
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what C is targeted by the PI-3K
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C3
phosphorylation here changes PIP2 to PIP3 |
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what does PDK-1 do
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phosporylates the PKB that is attached to PIP3
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does what does activated PKB activate
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GSK3
phosporylated form is the inactive form the active form causes inhibition |
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what does and activated Ras do
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it binds and activates Raf-1
Ser/Thr selective protein kinase |
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what does Raf-1 do
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it activates MEK
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what does MEK do
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it activates ERK
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what does ERK do
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it phosoporylates proteins such as important transcription factors like pp90(kinase that phosporylates S6)
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how is Ras's function in cancer patients
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highly mutated
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how is phosphatidylinositol 3-kinase activated
2 ways |
growth factor receptors
IRS-1 |
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what does PI3-K generate
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3,4,5 phosphatidylinositol PIP3 from PIP2
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what is a Plekstrin homology domain (PH domain0
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a region of protein that binds phosphoinositides and Beta/gamma units of G proteins as well protein kinase C
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where does PIP3 interact with proteins
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the PH domain
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what is attacked to the PIP3
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PKB protein kinase B
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what does PTEN do and one what molecule does it act
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terminates the signaling pathway
acts on PIP3 to change it back to PIP |
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what is central to insulins effects on metabolism
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PI3/PKB pathway
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what C is targeted by the PI-3K
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C3
phosphorylation here changes PIP2 to PIP3 |
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what does PDK-1 do
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phosporylates the PKB that is attached to PIP3
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does what does activated PKB activate
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GSK3
phosporylated form is the inactive form the active for phophorylates glycogens synthase to inactive form |
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what does active GSK3 phosphorylate
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Glycogen syntase
when this is phosphorylated it is inactive |
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what molecule stimulates GLUT4 to the plasma membrane
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PKB
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what is herceptin
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a monoclonal antibody against Her2
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what is Her2 involved in
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breast cancer
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what is Gleevec
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drug that selects against tyrosine kinases in leukemia patients and GI tumors
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what two drugs have been approved for use in colon rectal cancers
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Erbitux
Avastin |
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how are JAK activated
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by trans autophosphorylation
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what happens when cytokines bind to receptors that have little cytoplamic domains
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triggers a stepwise association with the subunits B1 and B2 to the receptor
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what comes along with the Beta 1 and 2 subunits
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JAK molecule
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what does JAK do?
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stimulates tyrosine phosphorylation of components of STAT transcription factors
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what is STAT
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transcription factors that JAK acts on, which are then translocated to the nucleus for gene regulation
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what happens to STAT after phosphorylation but before it enters the nucleus
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becomes dimerized
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what does cholera toxin effect
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the G protein
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what does the G protein do
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activates adenylyl cyclase
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what does adenylyl cyclase do
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catalyzes the reaction of ATP to Camp
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what are the 3 fates of Camp
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1. exported out of the cell
2. changed to 5'-AMP (cyclic amp phosphoidesterase) 3. changes PKA to an active form |
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what does active PKA do
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phosphorylates ser/threonine resisdues in many structure in the cell
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what characterizes a G protein
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the alpha subunit
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what do methyl xanthines do
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they inhibit cyclic amp phosphodiesterases
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T or F the cyclic AMP response pathway is not reversable at all
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F
reversable at all levels |
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what is the purpose of having multiple steps in the cyclic AMp pathway
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allows for amplification and cross talk with other pathways
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what is the response to TSH
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thyroid hormone synthesis and secretion
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what is the response to ACTH
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cortisol synthesis and secretion
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what is the response to LH
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progesterone secretion
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what is the response to adrenaline in the muscle
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glycogen breakdown
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what is the response to adrenaline in the heart
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increase in heart rate and force of contraction
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what is the response to adrenaline, ACTH, glucagon, TSH in fat
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triacylglyceride breakdown
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what is the response to glucagon
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glycogen breakdown
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what is the response to PTH
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bone resorption
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what is the response to vasopression
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water resorption
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what does inderal and propranalol do
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beta blockers (antagonist that prevent binding of adrenaline)
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what are Beta blockers such as inderal and propranalol used for
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treatment of hypertension, migraines and some cardiac problems
some performers use them for stage fright |
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what has a higer affinity value for B-catecholamine receptor antagonist or agonists
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antagonist is way higher
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what stimulates the exchange of GDP for GTP in a G protein
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binding of the ligand to the receptor
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what happens to the trimeric G protein when GTP is bound
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GTP causes a dissassociation of the A subunit
the A subunit bound with GTP is the active G protein |
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what causes the hydrolyzation of GTP on the Alpha sub unit of the G protein
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intrinsic GTPase of the Alpha subunit
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what is the subunit that the cholera toxin targets in the G protein
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the alpha subunit which specifically attacks the intrinsic GTPase so the signal stay on!
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what happens in the intestines when cholera toxin has done its worst
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Camp dependent activation of CL- channels leads to secretion of sodium and water
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how does C-amp activate PKA
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by disinhibition of the R subunits blocking the PKA binding sites
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why does PKA have two sites for binding
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two site will give a stepper response curve
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what are some important agonist in the Phosphotidyllinositol turnover signaling pathway
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acetylcholine
histamine vasopression angiotensin platlet-derived growth factor |
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what activates the Phosphotidylinositol turnover signaling pathway
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hormone receptor complex that activates phospholipase C
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what does phospholipase C do
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takes phosphotidlinositol 4,5 bisphosphate and adds H2o and separates them to yeild
diacylglycerol inositol 1,4,5-triphosphate |
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what directly activates phospholipase C
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activated G protein
activated growth factor receptor |
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what activates protein kinase C
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diacylglycerol
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what causes a release of Ca+ from the ER in the turnover signaling pathway
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inositol 1,4,5 triphosphate
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after PLC cleaves off diacylglycerol and IP3 what is the destination of these two molecules
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diacylglycerol=stays in the membrane
IP3= is soluble and head to the nucleus |
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what further degrades diacylglycerol in the the turnover pathway
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phospholipases A1/A2
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what is an alternative to further degredation of diacylglycerol besides the Phospholipase A1/A2
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conversion to phosphatidic acid by phosphorylation
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what molecule is able to mimic diacylglycerol in the activation of protein kinase C
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Phorbol ester tumor promoters
these are metabollically stable |
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what bond does Phospholipase A1 cleave in phosphotidylinositol
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the bond ester bond at carbon 1 right next to the fatty acid chain
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what bond does Phospholipase A2 cleave in phosphotidylinositol
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the bond ester bond at carbon 2 right next to the fatty acid chain
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what bond does Phospholipase C cleave in phosphotidylinositol
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the bond phosphodiester bond at carbon 3 right inbetween the O and P
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what bond does Phospholipase D cleave
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the bond in between the P and the O on the side of the head group
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when C2 is esterified with arachidonic acid in phophatidylinositol the molecule becomes a precursor for what
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Eicosanoids
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