Cell Physiology - Cellular signaling - Lec. 3 Flashcards
how do cells communicate with each other
receptors
signal transduction
processing the received signal
water-soluble signals
most common, binds to transmembrane proteins
lipid-soluble signals
diffuse through membrane, bind to intracellular receptors, transduce signal via change in gene expression
specificity
ability to receptor to only bind to a certain number of ligands (specific receptors, specific ligands)
affinity
strength of ligand binding to receptor
saturation
extent to which receptors are bound b ligand
competition
presents of other ligands which compete for binding sites
antagonist
no effect
agonist
effect
down regulation
lower # of target cell receptors, response to sustained high level of signal (- feedback), reduce cell response to frequent stimuli, mechanism is internalization
up regulation
increase # of target cell receptors, response to sustained low levels of signal (+ feedback), increase in cell response to low stimulization, occurs through insertion of receptor containing vesicles into the cell membrane
transduction of lipid-soluble signalling
response primary by nuclear receptors, causes gene expression.
1. diffusion across memebrane into cell
2. signals enter nucleus and bind
3. changes expression (mRNA) level of gene
4. mRNA abundance change effects change in protein leading to cellular response
two phases of water-soluble transduction
- binding of signal to receptor
- signals generated by receptor
protein kinases
enzymes that phosphorlate proteins
receptor tryosine kinases
name of sites where phosphorylation occurs
common mechanisims of water-soluble signalling
- recpetoc that function as ion channels
- receptors that function as enzymes
- receptors that interact with cytoplasmic kinases (Janus Kinases)
- receptors that interact with G-protein (g-protien coupled receptors)
g- proteins - what they do
couple receptors with effector proteins to generate 2nd messenger
g-protein sub groups
Gi - inhibits production of cyclicAMP
Gs - activates production of cyclicAMP
Gq - activates phospholipase C
How g-protiens work in general
ligand bind changes affinity of alpha subunit to GTP, GTP/GDP exchange causes dissociation b/w alpha and beta-gamma subunit complex, activated alpha subunit binds to effector protein to initiate cellular response
cAMP working and responses
activates cAMP-dependant protein kinases, PKA has many targets = elicit many responses
cAMP synthesis
ATP is catalyzed by adenylyl cyclase
cAMP breakdown
catalyzed by cAMP phosphodiesterase
How do signals cause the cytosolic Ca2+ concentration to increase
- activation of plasma memb.
- opening of Ca2+ channels on the ER memb.
- activate transport of Ca2+ out of the cell blocked by 2nd messenger.
how does increased Ca2+ concentration elicit a cellular response
typically via binding to proteins and activating them
Ways to stop signal transduction pathways
often occur at level of receptor activation
1. decrease conc. of signal (breakdown/uptake/diffusion)
2. change in receptor confomation (phosphorylation)
- changes signal binding affinity
- prevents further G-protein binding to receptor
3. receptor mediated endocytosis
