cell signalling Flashcards
If a cell had no input, could it survive?
What kinds of things can cell signals do?
No. Cells need signals from other cells to avoid apoptosis.
Signals let cells survive (always)
grow + divide
Differentiate (neural precursors)
No signals = apoptosis
How could cells send signals to each other?
(Pathways of intercellular signalling)
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Local:
Contact-dependent (Membrane-bound signal molecule from one cell to another)
Paracrine (local mediators released near cell to target cell)
Long-distance:
Synaptic (neurons)
Endocrine (Release hormones into bloodstream e.g. insulin pathway)
Why do some signalling molecules need carrier proteins?
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Signalling molecules are hydrophobic
They need to get through bloodstream first, which has water
(Eventually get to nucleus, where their intracellular receptor proteins are)
A signalling molecule binds to a protein on the surface of a cell
What is the protein called?
What property is the molecule likely to have? What is another name for that property?
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Cell-surface receptor protein
Molecule is hydrophilic, because it doesn’t go through membrane and does go through blood
Also known as lipophilic (dissolves in fats)
A cell-surface receptor protein activates an intracellular signalling pathway that alters protein function.
How fast is this process?
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Fast (sec to min).
Nucleus pathways (maybe more likely in intracellular receptors?) is slow
Intracellular molecules that get destroyed fast in reactions (rapid turnover) start to get made slower (decreased synthesis rate).
What happens to the concentration?
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Concentration decreases extremely fast
What is cAMP? Where do you see it?
A second messenger in signal pathways
Made from ATP
Concentration increased a ton with adenylyl cyclase
Serotonin (extracellular signal molecule) binds to a cell-surface receptor.
What happens?
Increase in cAMP (rapid turnover)
causes FAST upregulation of kinase A
How do you get PKC activated via second messengers?
- Signal molecules activates GPCR
- G-protein gets activated
- Sends signal to phospholipase C-B
- PI 4,5 bisphosphate activated
- PI Sends sugar to (triphosphorylated) to Ca2+ release channel. Ca2+ to PKC
- Also, PI activates diacylglycerol, which sends DAG to PKC
PKC now activated.
Needs Ca2+ and DAG.
Ca2+ needs inositol trisophosphate
DAG needs diacylglycerol
What two things can activate proteins?
Phosphorylation
GTP binding
What adds phosphate groups?
What removed phosphate groups?
Add: kinases
Remove: phosphatases
How are phosphorylation and GTP binding different?
List proteins involved
Phosphorylation: Protein kinase A adds phosphates from ATP, phosphotases remove phosphates
GTP-binding: guanine exchange factor (GEF) takes an entire GDP off and replaces with GTP, GTPase-activating protein (GAP) takes phosphates off that to inactivate
What kinds of cell surface receptors can there be?
What do they do?
ion receptors - let stuff through
g-protein coupled: attached to second messengers, which go do stuff
enzyme-coupled receptors: Activate themselves when bound
How would a g-protein coupled receptor originally get into a membrane after SRP binds to it while it’s made?
What specific protein types cause second messenger release?
Signal sequences through translocator proteins, etc multiple times (multipass)
Activated G-proteins and activated enzymes
How many subunits do G-proteins have?
3 (trimeric)
Where is calcium stored in the GPCR activation pathway?
How is it released?
ER lumen.
phosphoinositol (PI 4,5-bisphosphate) breaks into lipid + inositol (inositol 1,4,5-trisphosphate)
Inositol goes to ER lumen and opens Ca2+ release channel
What does DAG do and how is it activated?
Activates protein kinase C
Activated by the lipid part of broken phosphoinositol (diacylglycerol)
How does the CREB binding protein get activated?
What does it bind?
cAMP binds PKA
PKA goes through nucleus
PKA activates CREB in nucleus
CREB binds cyclic AMP response element (enhancer)
Gene is turned on
What does inactive PKA look like?
What happens when it’s bound by ___?
It has four subunits
Two are regulatory
Two are catalytic
cAMP binding to it causes both catalytic units to break off
What does phospholipase C do?
Why is this section of the pathway important?
It’s the one that activates PI(4,5)P2 and breaks it into the two products that end up binding PKC
Shows that G-proteins can do stuff through both proteins and lipids in the bilayer
What does calcium do?
What are some examples?
Does all kinds of stuff in the cell to mediate things
Ex bind calmodulin
Ex make calcium waves
What does CaMKII stand for?
What does it look like / what domains does it have?
What does it do?
Calcium/calmodulin dependent kinase
Two stacked rings of 6 subunits each. Each subunit has a hub domain, kinase domain, linker, regulatory segment, phosphorylation site.
It’s like a memory trace of a Ca2+ pulse.
How does CaMKII work to store a memory trace of Ca2+?
1) Ca2+ / calmodulin binds to to the regulatory segment of a subunit
2) The kinase domain of the subunit changes conformation and grabs a phosphate group
3) The phosphate group binds to the phosphorylation site
4) Other parts automatically get phosphorylated, because the kinase domain is still pulled out.
5) CaMKII stays like this until other phosphotases manually take out phosphate groups
What binds to ER lumen to release calcium?
How does this happen?
IP3 binds after release from PI-4,5-bisphosphate
This binding opens a Ca2+ channel
This causes a cascade of channels to open
When enough calcium is outside, channels start to close
release calcium waves
