Cell Signalling Flashcards
EC50
Ligand concentration that results in 50% activity of the receptors
Kd
Concentration that ligand occupies 50% of receptors
Binding vs activity
Hormone induces adenylyl cyclase activity in proportion to its binding ability.
Agonist
Binds and activates receptor
Antagonist
Bind receptor, prevents activation. Itself has no effect on receptor activity
Partial agonist
Bind and activate receptor to lesser extent than agonist
Inverse agonist
Binds active receptor and blocks the activity
Rate limiting step in G proteins
Catalysed release of GDP
Gs induces
Increase adenylyl cyclase, Ca and cAMP
Gi induces
Decrease adenylyl cyclase, Ca and cAMP Increase PLC (Ga and GBy)
GQ induces
Phospholipase C
Classification of GPCR
Class A - rhodopsin
Class B - secretin
Class C - glutamate
Other - adhesion R, frizzled/ taste 2
How to measure G protein association in cells
FRET - Fluorescence resonance energy transfer
Effect of cholera toxin
Inhibits GTPase (NAD dependent)
Effect of pertussis toxin
Prevents activation of Gi by receptor
Phospholipase C activated by two pathways
PTX insensitive - Gaq
PTX sensitive - Gai (direct activation by GBy, + Gai is called conditional)
Compound that blocks inositol recycling
Lithium
Molecules that can bypass receptor ligand and activate PKC
Phorbol
Ca ++ iodophors
CAMP -> PKA ->
Activate metabolic enzymes
CREB - cAMP response element binding protein.
Ca-calmodulin steps
Ca binds calmodulin. Conformational change. Binds inactive Calmodulin dependent protein kinase. Causes auto phosphorylation. Now fully active.
RTKs regulate
Cell proliferation
Differentiation
Metabolism
SH3 binds..
Pro line rich targets. Eg, sos
RTK process
Ligand binds
Dimerisation
Trans auto phosphorylation
Ras is required for..
DNA replication / entry in S phase
GEF
Guanine nucleotide exchange factor
GAP
GTPase activating protein
Map kinase pathway
Raf binds Ras.
Raf now membrane bound. Activates MEK. Activates ERK. Activates transcription factor.
What can stimulate Ras
GPCR ( PKC )
Arrestin
TKRs
Homologous desensitization
Ligand stimulation causes reduced response of active receptor
GRK - G protein receptor kinases, phosphorylate ser/thr on c terminal and c3.
Heterologous desensitization
Ligand stimulation causes decreased responsiveness of inactivated receptors.
PKA
Give two formulas need for ligand hormone stuff
Get it right son.