Signal Transduction 1 Flashcards
Why is it important understanding signal transduction key:
a. cause of abnormalities d/t disfunciton w/ signaling pathway
- . causes disease
- understanding pathways allows us to devo drug therapies
How do cells recieve and respond to signals
cells recieve sigs by interacting with cell signal molecues that transude signal and INDUCE a respose as result of signal
Response to signal transduction often involves
activation of genes
Three requirements to inducing cell response
- Sginals cross membrane
- Signals transduced through cytoplasm–> nucleaus
- Genes need to get expressed
What allows cellular response to occur
receptors and intracell signalling molecues
Local mediators secreated by signal cell and recieved by surrounding target
paracrine signaling on neighbro
Mediators secreated and recieved by same cell
autocrine
NTs secreated by pre-synaptice nerve to cleft, recieved by post cell that is nerve or muscle
Synaptic signaling
Hormones secreated into blood stream–> hormones to distant target cells
Endocrine signalin
signaling molecule= transmembrane protein, the extracell domain acts as ligand for receptor on target cell and target cell and signal cell in close contact
Signaling by plasma-membrane bound molecules
These receptors bind small hydrophobic molecules like steroids, vit D, thyroid hormone, retinoids
Intracellular steroid receptors
Two unique characteristics of intrcell steroid receptors
Receptors = intracell and interact with thei ligand in either cytoplasm or nucleus
Receptors are ligand activated transcription factors
Receptors are ligand activated transcription factors
Intracell steroid receptors
Receptors = intracell and interact with thei ligand in either cytoplasm or nucleus
Intracell steroid receptors
Three domains on steroid receptors
- hormone binding site
- DNa binding domain
- Transcription activating domain
What happens when an intracellular steroid receptors binds a steroid hormone
Receptors dissociates from inhibitory proteins, thus DNA binding domain can interact with DNA
Glucocorticoid receptor is example of
intracelllar steroid receptor
Glucocorticoid receptor binds:
coritsol once passes through membrane
Cortisol is steroid hormone and is thus
hydrophobic
How does cortisol get around in the bloodstream
Gets a ride from corticosteroid binding globulin to keep it soluble in blood stream
What is the function of corticosteroid binding globulin
gives cortisol a rdie through blood steram bc it’s hydrophobic and drops it off at target cell
Where is the location of the glucocorticoid receptor that cortisol binds to?
it’s in the cytoplasm waiting for cytosol
Thyroid receptor and retiod receptors are located
in nucleus
Glucocorticoid receptor exsist in acitve/inactive complex in cytosol as it’s associated with
inactive
heat shock protein 90
whats teh purpose of heatshock protein HSP90?
binds to GR in the cytosol and dissociates when cortisol comes along
Cortisol getting through membrane once it dissociates from CBG is an active or passive process?
passive
once cortisol binds to GR, what happens to GR
undergoes conformational change and dissociates from the cytosolic proteins that were inhibiting it
GR bound to cortisol heads to:
nucleus
In order to hook up with the DNA in the nucleus, the active GR-cortisol must:
dimerize
Dimerized GR-cortisol binds with: high/low/intermediate affinity to GRE
high affinity
GRE in DNA is:
Glucocortocoid response element
Glucocorticoid response element is variable/constant
constant region
GRE is an example of :
hormone response element
Hormone response elements are DNA sequences that bind
steroid receptos
Where do steroid receptors bind to hormone response elements?
near promoter of target gene
What is the result of binding an activated steroid receptor to a hormone response elelment on DNA target gene?
Can increase OR decrease transcription of target gene
Glucocorticoids are useful for:
anti-inflammatory agents d/t gene regulation
Ion channel linked receptor is
membrane receptor
G-coupled protein receptor is
membrane receptor
EnZ linked receptor is
membrane receptor
Receptors for Ach, GABA, serotonin and glycine have how many subunits and are what tupe of receptor
ion-channel linked or ionotropic receptors
5 subs
serotonin uses what kind of receptor
ligand gated: 5 subs
GABA uses what kind of recepto
ligand gated w/ 5 subs
Ach uses wht kind of receptor
ion-gated or ligand gated with 5 subs
how many subunits does the Glutamate ligand have
4
Ionotropic receptors
directly control opening and closing of channel
directly control opening and closing of channel
Ligand gated
Activation of ion channel linked receptors are slow or rapid activating
rapid with rapid signaling
First ion channel to be purified, sequence determined, reconstituted in lipid bilayer
nicotinic
Nicotinic subunits inclue:
alpha 1, and 2, Beta, gamma, delta
What binds to nicotinic receptors?
Ach
where does Ach bind to on nicotonic receptors
on the Alpha units which causes opening
What happens when Ach binds to alpha subs on nicotinic receptors
selective influx of CATIONS
Cation influx as result of Ach binding to nicotinic receptors induces:
depolarization and excitation
Ach is what kind of NT
excitatory: causes depoarlization
Where are nicotinic recpetors located
Neuromusclura jnx
Peripheral auntonomic nervous system
CNS
What is our primary postsynaptic INHIBITORY NT in the CNS
GABA or gamma-maniobutric acid
When GABA binds to receptor:
Cl- channels open = influx of Cl—> hyperpolization
GABA opens up:
Cl- channels
influc of Cl- d/t GABA cuases what kind of response
hyperpolarizationg or inhibitory
Barbituates and benzodiazepine bind to GABA to
potentiate inhibitory action of GABA
these receptors regulate effect of: NTs, light, odorants, hormoens, extracell messengers like GFs and cytokines
G-coupled proteins
GPCR is a protein coupled receptor that psses through membrane how many times
7
The GPCR is for:
The Heterotrimeric G protein is for:
The Effector is our:
- provides specificity
- Coupling or transducer
- catalytic componenent to generate 2nd messenger
What links our GPCR to the effector enZ
the heterotrimeric G protein (has the alpha subunit that dissociates from teh beta/gamma via GTP–>GTP)
Transducer of the GPCR system
heterotrimeric G protein
What part of GPCR sytem provides specificiy?
GPCR
Heterotrimeric protein has two states:
GDP bound =
GTP bound =
GDP = inactive GTP = active
Which subunit of heterotrimeric protein binds to GTP and interacts with effecto
Alpha subunit
The alpha subunit on G coupled protein resposible for
hydrolyzing GTP–> GDP via GTPase activity
which subunit on G protein has GTPase activity
alpha sub
What part of G protein is bound to membrane
beta/gamma and inhibits alpha subunit
When a Gprotein is activated by a GCPR we go from an inactive to active state…how?
releases the GDP from alpha subunit and picks up GTP on alpha subunit–> alhpa dissociates
When alhpa is bound to GTP what will it do
dissociate from beta/gamma–> go to effect to transude the message
How are heterotrimeric G proteins classified
by the type of alpha subunit in heterotrimer
Different Galpha subinits will
target different receptors and target dif effectors
G-alpha-S will:
stimulate adenylyl cyclase (on test)
G-alpha-i will:
inhibit adenylyl cyclase (on test)
G-alpha-q will:
activate phospholipase C (on test)
which alhpa sub will activate adenylyl cyclase
G-alpha-a
Which alpha sub will activate pholspholipase C
G-alpha-q
which alpha sub will inhibit adenylyl cyclase
G-alpha-i
