General Principles of Cell Communication Flashcards
What are the 3 types of cell signalling?
Endocrine - widespread, effects many cells in the body
Autocrine - signal feeds back onto same cell
Paracrine - two cells close, simple diffusion, short distance
All receptors do 2 things
Recognise a specific signal
Initiate a cellular response
Explain the functionality of receptor tyrosine kinases
Responds to growth factors Act in dimers Kinase = phosphorylates intracellular proteins 1st messenger binds to receptor Stimulates enzyme Phosphorylates proteins
What is the result of some mutations in receptors?
constitutive activity
activation in the absence of a ligand
If the ligand is a GF –> cancer
Example of a ligand-gated ion channel
Why is it named this?
How does it work?
nicotinic acetylcholine receptor (nAChR)
5 subunits, Na+ pore through centre
Binds ACh on post-synaptic membrane, leads to depolarisation
Nicotinic - nicotine mimics ACh in brain –> addiction
Example of a GPCR
Muscarinic acetylcholine receptors
Muscarine found in mushroom mimics ACh
Define G protein and outline structure
heterotrimeric GTPases that transfuses effect from receptor to effector
7 transmembrane helices
Guanine nucleotide regulatory binding protein
Which organisms to not have GPCR’s?
bacteria
Outline the steps involved when a ligand binds to a GPCR
1) Ligand binds to GPCR
2) GPCR undergoes conformational change
3) alpha subunit exchanges GDP for GTP
4) alpha subunit detaches –> effect
5) GTP hydrolysed to GDP by GTPase within the subunit
6) alpha subunit reassociates
How does the cholera toxin interact with GPCR’s to produce it’s effect?
decreases activity of GTPases
GTP binds irreversibly
prolonged activation of Gs
increased cAMP
How does bordatella pertussis interact with GPCR’s to produce it’s effect (whooping cough)?
prevents GPCR interacting with g-protein (Gi)
No GDP dropping off
Prevents Gi inhibition so cAMP increases
What converts ATP into cAMP?
How is the cAMP signal switched off?
adenylyl cyclase
cAMP phosphodiesterase converts cAMP into 5’AMP
In what 2 ways can you increase cAMP?
activate adenylyl cyclase
inhibit cAMP-PDE
What does cAMP do?
activates protein kinase A (PKA)
phosphorylates proteins
What is phospholipase C and where is it found?
Effector of a GPCR
An enzyme
Phospholipid bilayer
What happens when PLC is activated?
two 2nd messengers are formed
InsP3 - Inositol-1,4,5-trisphosphate
DAG - diacylglycerol
Which type of Gprotein relay signals to phospholipase C?
Gq and G11
What effect does InsP3 have?
What effect does DAG have?
InsP3 causes the release of calcium from intracellular stores
DAG activates membrane bound protein kinase C
These both lead to protein phosphorylation/dephosphorylation
What is UDP?
What is UDP-Glc?
uridine diphosphate
glucose bound to UDP - the metabolically activated form of glucose
What enzyme catalyses this reaction?
glycogen(n) + UDP-Glc –> glycogen(n+1) + UDP
glycogen synthase
What enzyme catalyses this reaction?
What is the second product?
glycogen(n+1) + Pi –> glycogen(n) + Glc-1-P
glycogen phosphorylase
glucose-1-phosphate
What do protein kinases do?
What do protein phospatases do?
- adds phosphate
- removes phosphate
2 pathways in the enzyme cascade for glycogen metabolism
cAMP activates cAMP dependent protein kinase (PKA)
activates glycogen phosphorylase kinase
activates glycogen phosphorylase
–> glycogen
OR
cAMP activates cAMP dependent protein kinase (PKA) which activates glycogen synthase
Effect of increased cAMP on glycogen metabolism
activates glycogen breakdown
inhibits glycogen synthesis
Effect of decreased cAMP on glycogen metabolism
inhibits glycogen breakdown
Activates glycogen synthesis
