Signalling Flashcards
Signal transduction pathway (5 steps)
Release of primary messenger
Reception of primary messenger
Delivery of messenger inside cell by second messenger
Activation of effectors that alter physiological response
Termination of the signal
What does GPCR stand for?
G-protein coupled receptors
Most common mutation in cancer
Mutation in Ras
What does GEF stand for?
GDP exchange factor
What facilitates the change from GDP to GTP?
SOS (GEF) which binds to Ras
What is the first messenger?
Extracellular signal that activates a receptor from the outside of the cell
What is the second messenger?
low MW metabolite or inorganic ion that changes in concentration due to the effector enzyme
Where is Glut 4 especially present?
In the cytoplasm
Is there a high or low amount of second messengers during the resting state of the cell?
Low
Common second messengers
Calcium ion
Diaclyglycerol
Cyclic GMP
Cyclic AMP
Inostiol 1,4,5-triohosphate (IP3)
What activates the formation of cyclic nucleotides?
Adenylyl cyclase
What deactivates the formation of cyclic nucleotides?
cAMP phosphodiesterases
What does PI 3-kinase produce?
PIP3
Phosphorylates inositol (PIP2) in the 3rd position
What kind of messenger is calcium?
Second messenger
Is signal transduction specific?
Yes very specific
What is the Ka when the affinity is high?
Low
What is desensitisation?
When receptors are activated it triggers a feedback that shuts off the receptor or removes it from the cell surface
What is divergence?
When a receptor activates two or more pathways
What is G-protein activated by?
Binding of GTP
What are the subunit of G protein?
Alpha
Beta
Gamma
What is 7TM?
7 transmembranos receptor
What does GTPase do?
Removes a phosphate making GTP GDP
Does GEF favour GTP or GDP?
GTP
Does GAP favour GTP or GDP?
GDP
What are adrenergic receptors?
Protein receptor in the plasma tha bind epinephrine
What is the target tissue of epinephrine?
Muscle
Blood vessles
What kind of stress is epinephrine in “charge” of? Long term or acute?
Acute stress
What does cyclic AMP activate?
PKA
What is an agonist?
A molecule that is different than the natural ligand but produces the same effect
What is an antagonist?
Analog that binds the receptor and blocks the effects of the agonist and natural ligand
Which subunit of PKA does cyclic AMP bind to?
Regulatory subunit
2 subunits of PKA
Regulatory and inhibitor subunits
What are kinases all phosphorylated by?
Ser and Thr (but specific ones, in a specific sequence (consensus sequences)
What does CREB stand for?
cAMP Response element binding protein
What does CREB do?
Alters the expression of specific genes regulated by cAMP
What are Gi proteins?
Inhibitory G protein
What does cholera toxin block?
GTPase activity of Gs
Where is calcium stored?
In the ER
What opens calcium channels?
IP3
What is released when PIP2 is cut?
IP3 (polar end group)
What does IP3 act as a second messenger to release?
Calcium
What happens to Fura-2 when it binds to calcium?
It becomes florescent
What is Fura-2 used to when bound to calcium?
Determine the intracellular calcium concentration as it is proportional to how fluorescent it is
What is calmodulin?
An important calcium modulator
Regulatory protein
What 2 domains does receptor tyrosine kinases have?
Extracellular ligand binding domain
Cytoplasmic Tyr kinase domain
What does RTK stand for?
Receptor tyrosine kinases
Why is Rat called a small G-protein?
Because it is not coupled to the receptor
What kind of receptor is the insulin receptor?
Tyrosine kinase receptor
Which subunits does insulin bind to in inulin receptors?
Alpha subunits
What kind of dimers does Tyrosine kinase receptor have? and how many?
2 homodimers
What is the SH2?
The modular protein domain that recognise phosphorylated tyrosine present in a specific consensus sequence
What is PKB also called?
AKT
Are the dimers of the EGF receptors always united?
No they have to go through dimerisation
