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71 Cards in this Set

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What receives the signal in most cases of cell communication?
a receptor protein on the target cell
What are the 4 mechanisms of cell communication?
1. Contact Dependent Signaling
2. Paracrine Signaling
3. Synaptic Signaling
4. Endocrine signaling
What is contact dependent signaling?
-relatively rare
-no chemical released
- cells have to come into very close contact
- Important during embryonic development
What is paracrine signaling?
-common
- can target multiple, neighbouring cells
- doesn't go very far (local)
-signal is released by exocytosis and acts on multiple neighbouring targets (paracrine)
- or on the signaling cell itself (autocrine)
- acts as a feedback mechanism that allows the cell to control the signal
What is the difference between Paracrine and autocrine?
Paracrine- in paracrine signaling, when the signal acts on multiple neighbouring targets

Autocrine: when the signal acts on the cell itself.
- feedback mechanism that allows the cell to control the signal
What is synaptic signaling? Where does it function?
- Only functions on cells of the nervous system
- equivalent to "face to face conversation"
- signal is produced by a neuron and released at a synapse; acts on a single postsynaptic target
What is endocrine signaling?
- When a hormone is released by exocytosis, it is released into the blood stream and can reach cells that are far away
- acts on multiple cells
What kind of cell produces hormones?
an Endocrine cell
What types of signaling target multiple cells? What kind target single cells?
Multiple cells
- Paracrine Signaling
-Endocrine Signaling

Single cell
- Synaptic signaling
-Contact dependent signaling (I'm only 90% sure about this)
- What are the types of signaling molecules? Which is most common? Least common?
-hydrophilic (most common)
-hydrophobic
-gases(least common)
List examples of hydrophobic signaling molecules. What are they generally?
generally, they are proteins, peptides, derivative amino acids, and small organic molecules

Acetylcholine
- a neurotransmitter

Adrenaline
- small, organic molecule that functions as a hormone

Growth factors
- most often used in paracrine signaling
In what kind of signaling are growth factor proteins commonly used?
Paracrine signaling
Signaling molecules are _________ in animal phyla
conserved
Give an example of a hydrophobic signaling molecule
Steroid hormone
Give an example of a gas signaling molecule
Nitric oxide
How does a hydrophobic signal or gas signal bind to a receptor?
-since it is hydrophobic, it can permeate the target cell and bind to either cytosolic receptors or nuclear receptors

-goes right through the cell membrane
what kind of signal type are protein kinases (usually)?
Hydrophobic
How does a hydrophilic signal bind to a receptor?
-hydrophilic signals cannot permeate the membrane.

- bind to cell surface receptor, making them an extracellular receptor

1. binds to surface receptor
2. alters the intracellular protein, which acts like an intermediate protein (cascade effect)
3. Target protein is then affected
How is the target protein effected in extracellular signaling? What type of signal does extracellular signaling
1. binds to surface receptor
2. alters the intracellular protein, which acts like an intermediate protein (cascade effect)
3. Target protein is then affected

- signal type: hydrophilic
If the target protein of extracellular signaling is a metabolic enzyme, what happens?

If it's a gene regulatory protein?

if it's a cytoskeleton protein?
Metabolic enzyme- would alter metabolism

Gene regulatory protein- altered gene expression

cytoskeletal protein- altered cell shape or movement
What determines the response that an extra cellular signal will cause (i.e. Acetylcholine)?
Determined by type of cell-surface receptor on diff. cells
ex.
A) in a heart muscle cell
- Acetylcholine binds, causes muscle to elongate then relax.
-decreased rate and force of contraction
B) Salivary gland cell
- Acetylcholine binds, causes secretion
C) Skeletal muscle cell
- Acetylcholine binds to receptor on muscle
- contraction
What are the properties of fast and slow responses in cell signaling?

In other words, what makes a fast response fast, and a slow response slow?
Fast response: involves changes in existing proteins

Slow response: requires new protein synthesis
Steroid Hormone:

- What is it derived from?
-how does it reach the target cell?
-what are its important functions?
-Derived from cholesterol
- dispersed through blood, (endocrine signaling)
-Functions: controls metabolism, immune function, development of male/female sexual characeristics
What is the process of a steroid hormone causing translation of a gene? (general, from receptor binding to translation)
-Steroid binds to receptors in the cytosol, then moves to nucleus
OR - steroid binds straight to nucleus receptors

- in nucleus, steroid receptor complex binds to DNA, which turns on gene expression (that is a slow response)
- binding causes genes to be transcribed
-leads to translation
What type of protein are steroid Receptors?
DNA=binding proteins
What part of steroid receptors is highly conserved?

In other words, what is the same in all Steroid receptors?
DNA binding domain
What is the DNA binding domain of steroid receptors consist of?
Two zing fingers that bidn to specific DNA sequences called Hormone Response Elements
What are Hormone Response elements?
DNA sequences to which the DNA binding domains of Steroid Receptors bind.`
What makes a steroid receptor inactive?
The nuclear localization signal is bound by an inhibitory protein ( a chaperone)
What are the parts of an empty steroid receptor?
Ligand binding domain
transcription activating domain
DNA binding domain
What does the steroid receptor look like as soon is it is activated?
-A ligand is attached
- Coactivator proteins are attached to the ligand-binding domain and transcription activating domain
- Only the DNA binding domain is exposed
Once the hormone is in the steroid receptor, how do Steroid hormones activate gene expression? (specific)
1. Receptor-steroid-hormone complex activates primary response genes.
2.Primary (early response) genes are transcribed
3. Proteins encoded by these genes (primary response proteins) turn on expression of secondary delayed response genes
4. Secondary response proteins synthesized
What are the three types of cell-surface receptors?
1. Ion-channel linked receptors
2. G protein-coupled receptors
3. Enzyme-linked receptors
what are the structural characteristics of GPCRs?
7 transmembrane domains

N- terminal in extracellular matrix, C- terminal in side the cell

3 loop of intracellular loop is bigger than the others
What part of GPCR is important for binding the extracellular signals? the intracellular signals?
extra-cellular: N-terminal

Intra-celular: Cterminal and 3rd intracellular loop
What intermediate is needed for GPCR to activate a target?
a G-protein
What is an orphan receptor?
a receptor for which the gene exists, and it is expressed, but we don't know what activates it

many are probably activated by smell/taste
What is the structure of a G-protein? What are its general physical properties?
-Trimeric, has three subunits (alpha,beta, gamma)
-has GTPase activity
-lipid-anchored membrane protein
what does the alpha subunit do in G-proteins?
it binds and hydrolyzes GTP and GDP
What are the three major classes of G proteins?
Gs
Gi
Gq
What does the inactive form of G protein look like compared to the active form?
Inactive is trimeric, and has GDP

Active has dissociated subunits, GTP
How do the three subunits of the G protein dissociate?
Alpha splits from (beta and gamma), all three remain attached to the membrane
What is the first thing that happens when a signal binds to GPCR?

Then what?
A conformational change in the receptor occurs, causing GPCR to have a higher affinity for G protein/binds more tightly to g protein

Then, G protein undergoes a conformational change, causing it to replace GDP with GTP

After this, protein is fully activated?
Which subunit(s) of g protein act like an on/off switch? How?
G alpha subunit, because it binds to a target protein which creates altered protein activity (on)

after a while, G alpha subunit hydrolyzes GTP and dissociates from the target (off)
What happens to G alpha subunit once it dissociates from its target protein?
It re-associates with G beta/G gamma subunits, making the G protein inactive once more.
What is the most common target of G proteins?
Adenylate Cyclase enzyme
What activates adenylate cyclase? what inhibits it?
Gs alpha activates

Gi alpha inhibits
what activates phospholipase c-beta?
Gq alpha
What produces cyclic AMP (cAMP)?
adenylate cyclase
When would you see cAMP in a cell? when would you not see it? Why would you start/stop seeing it?
you would see it when the enzyme Adenylate cyclase is activated.

you would stop seeing it once the signal for Adenylate cyclase activation has ceased (once GCPR is not binding to a signal)
- because cAMP is quickly destroyed by phosphodiestherase
What does cAMP activate?
Protein Kinase A (PKA)
What is the structure of Protein Kinase A (PKA)?
4 subunits, 2 catalytic, 2 regulatory
What role do the subunits of PKA play?
they bind to cAMP (4 cAMP are needed to activate a protein kinase)

once cAMP is bound, it causes the dissociation of PKA complex, which releases the catalytic subunits that can phosphorylate other proteins
how many cAMP are needed to activate a PKA?
4
What's an example of a serine-thrionine protein kinase?
PKA
What enzyme has broad specificity and catalyzes reactions at serine/thrionine residues?
PKA
is cAMP fast or slow? why?
fast, doesn't need to do protein synthesis
Give an example of an intracelllular second messenger. What makes it an intracellular second messenger?
cAMP, because the 1st messenger would be the extracellular signal that causes the formation of cAMP
- then cAMP is the second, because it then activates PKA

-cAMP necessary because the hydrophilic 1st signal cannot get in the cell
When would cAMP be considered fast response?

slow response? what happens here?
cAMP is fast during its regular activity in activating PKA, because no proteins need to be synthesized.

cAMP is slow when it stimulates gene expression
- less common
- happens when PKA can get into the nucleus via nuclear pores
- causes the nuclear protein CREB to be phosphorylated
-CREB is a gene regulatory protein, which causes new proteins to be syntehsized when it is phosphorylated
What is a CREB?
a nuclear, gene-regulatory, protein that is phosphorylated by PKA via slow response (when PKA goes straight into nucleus, stimulated by cAMP)
What are the 4 ways a cell can stop the response to a signal in G-protein coupled receptor signaling?
1) no more signal is made, means no more G-protein is made, which causes a cascade
2) If the G-alpha subunit turns itself/g-protein off by hydrolyzing GTP
3)if the enzyme that destroys cAMP (phospho-diestherase) becomes active
4) if the protein phosphatases that remove phosphates become active
how does signal desensitization occur? Why does it occur?
Occurs in response to a signal that continuously keeps being delivered (for example by a stress related hormone)
- receptor is constantly full of signal, keeps being activated, needs to be "quieted"
- after some time, receptor becomes desensitized by repeated ligand stimulation
-if the signal is present in the receptor for too long, the receptor will be phosphorylated, causing a conformational change
What does Adrenaline stimulate in the muscle and liver?
- glycogen phophorylate
What mediates the effect of Adrenaline stimulus? Why?
a GPCR called beta-adrenergic receptor
- Because the hormone is outside of the cell, it needs a GPCR to send the signal inside
what is the path of the Adrenaline signal in turning on Glycogen Phosphorylase?
1. Adrenaline binds to beta-adrenergic GPCR (associated with Gs
2.G protein activated
3.Adenylate cyclase activated
4.causes production of cyclic AMP
5. Makes PKA active
-PKA, although it has broad specificity, does not recognize Glycogen phosphorylase, so there needs to be an intermediate
6.PKA activates phosphorylase kinase (PK)
- via phosphorylation
-PK specifically phosphorylates Glygogen phosphorylase
7. PK phosphorylates GP, activates it
8. Glycogen brokedown into Glu-1-P
What breaks down cAMP immediately after it is produced (pretty much immediately after)?
cAMP phosphodiestherase
How does signal amplification occur?
it is the by-product of signal cascade
- everytime a reaction step occurs, you intensify teh signal because more and more molecules are involved
ex. PKA activated
- 1 molecule PKA, phosphoryaltes many PK
- each PK phosphporylates many GP
what are several examples of intracellular second messengers?
cAMP

Calcium

inositol triphosphate, GMP
explain how Calcium acts as a an intracellular second messenger.
Calcium increases rapidly in stimulated cells, proteins activated
ex. Calcium/calmodulin-dependent protein kinases (CaM kinases)
ex. Protein Kinase C (PKC)
ex. Calcineurin (Phosphatase)
ex. Troponin (actin-binding proteins)

Gq and phospholipase C-beta signaling pathway
- uses inositol phospholipid.Calcium pathway
- used in control of regulated secretion/exocytosis
-phospholipases c-beta cleaves phosphoinositol biphosphate (PIP2)
- reaction produces inositol triphosphate (IP3) and Diacylglycerol
What is IP3 (Inositol triphosphate)? What does it do?
a product of the Phospholipase C-Beta signaling pathway
- IP3 travels to ER and opens channel of ER membrane
- ligand gated channel
-Calcium released into cytosol
what are all thre major pathways in eukaryotic intracellular communication?