lecture 2 Flashcards
describe timing of cell proliferation
occurs at same time across embryo
what does intracellular signaling do to cell proliferation
controls/synchronizes mechanism across 10k+ cells across embryo
describe regulation of cell proliferation
tightly regulatedw
what do signaling pathways do for cell prolfieration
control when, where, how cell division occurs
what happens if pathway in cell that tells cell now isn’t the time to divide is mutated
cell is not prevented from dividing, cancer happens
describe cancer
DNA in cells become mutated, proteins that control when cell divides or not aren’t active, cells are dividing when they shouldn’t
what happens when pathways regulating cell movement are mutated
metastasis; tumor metastasizes across the body
basically what regulates cell division
signaling
what is human fibroblast
maintains tissue homeostasis
what does fibroblast need to do
signals in env. to tell it what to do; awaits signals to be activated
PDGF
platelet derived growth factor
how is PDGF introduced
secreted in extracellular environment; diffuses till it reaches fibroblast
what happens when PDGF reaches fibrobalst
binds to receptor in plasma membrane
what does this binding event cause
chem rxn inside of cell that triggers mechanism of cell proliferation
what is every step of this mechanism controlled by
intracellular signaling
what is example of extracellular signal molecule
PDFG
what is plasma membrane generally
barrier to transmission of info from outside to inside of cell
what is plasma membrane insoluble to
water insoluble
what is PDGF soluble to
water soluble (hydrophilic)
where is PDGF secreted
into extracellular environment so it can diffuse till it reaches target
what does this mean for PDGF in membrane
can diffuse but can’t pass thru plasma membrane
what is needed for signaling molecules to pass thru
receptor protein/plasma receptor
key property of receptor protein?
spans the plasma membrane; part of it is on outside, part is anchored in lipid bilayer, part is inside cell
what happens when growth factor binds receptor
triggers conformational change in receptor protein,
what does this binding activate
signaling pathways on cytoplasmic side (inside) of plasma membrane
what does the conformational change do
switches it from off state/inactive to active
what happens when any protein becomes active
it’s able to bind its downstream targets and activate them
what’s at the end of the pathway
effector proteins
what happens to effector proteins as signals are transmitted
they get farther and farther from plasma membrane
4 types of extracellular signals/ligands
paracrine signaling, endocrine signaling, synaptic signaling, contact-dependent
paracrine signaling
signaling ligand is secreted but never enters bloodstream, just interstitial [short range]
example of paracrine signaling
PGDF
endocrine signaling
signaling ligand travels through bloodstream [long distance]
example of endocrine signaling
hormones
contact dependent signaling
ligand is expressed on surface of cell (outside environmnent), not released; cell-cell contact dependent
what happens in contact-dependent signaling
when target cells bind ligand, requires contact of two cells
synaptic signaling
neurotransmitter
what receptors do signal molecules bind to
cell-surface receptors or intracellular receptors
what types of signaling do these receptors apply to
contact dependent and paracrine signaling
describe signaling molecule of cell surface receptors
hydrophilic; can’t enter membrane, that’s why you need cell-surface receptor that spans whole membrane
describe signaling molecule of intracellular receptors
small, hydrophobic
why is hydrophobic molecule a problem
once secreted they have trouble navigating through blood; need carrier protein that’s water soluble
what do we deal with most of the time
receptors at surface of plasma membrane
example of same ligand triggering different effects depending on cell
acetylcholine
what effect does acetylcholine have on heart pacemaker cell
decreased rate of firing
what effect does acetylcholine have on salivary gland cell
secretion
what effect does acetylcholine have on skeletal muscle cell
contraction
what does acetylcholine do
binds to G protein coupled receptor (specific class of receptor)
describe GPCR
huge, passes plasma membrane 7 times
what does acetylcholine do in heart pacemaker cell
acetylcholine ligand binds to receptor, triggers change in frequency of firing pacemaker cell, slowing heart beat
what does acetylcholine do in salivary gland cell
binds to receptor, triggers component in rate of secretion of saliva
why does acetylcholine does diff stuff in cell
these cells don’t express same types of pathways
three major classes of cell-surface receptor proteins
ion-channel coupled, G-protein coupled, enzyme-coupled receptors
GPCR
pass membrane 7 times, when inactive, held together in heterotrimeric complex
enzyme-coupled receptors
always receptor tyrosine kinases
ion-channel coupled
flow of neurons from inside to outside of cells
how do cell-surface receptors relay signals
thru intracellular signaling molecules
phosphorylation is
post-translational modifications
what can phosphorylation control
protein activity, intracellular signaling; basically a way for proteins to control their activity
describe phosphorylation
signal comes in, activates receptor, activates kinase associated w/ it
what happens when kinase is activated
binds to downstream target, grabs floating ATP, plucks a phosphate group, covalently binds to downstream target
what does it mean if there’s a way to activate signaling pathway
there’s a way to inactivate signaling pathway
if cells can’t regulate (turn on or off), what happens
bad shit
what turns off the pathway in phosphorylation
second enzyme (phosphatases)
job of phosphatases
to hydrolyze the phosphate bond to proteins and release it
what does kinase do
adds phosphate to activate it
what does phosphatase do
removes phosphate; everything gets returned
what’s another nucleotide that controls intracellular signaling
GTP
what happens when protein bound to GDP form
(2 phosphates); inactive
what happens to activate receptor
signal comes in, GDP kicked off into cytoplasm (released), G protein is gonna bind to next guanine nucleotide it bumps into (GTP)
what does GTP binding do
triggers conformational change within G protein that allows it to bind to next target
GDP version
off
GTP version
on
what are G proteins always bound to
nucleotide
what happens in GTP hydrolysis
P leaves, GDP remains, turns it off
what happens when G protein turned on
GDP is released (kicked off), new molecule of GTP binds in its place [activated]
what happens to turn G protein off
GTP remains bound, just converted in GDO and hydrolyzed; phosphate leaves
GEF
enzyme; guanine exhcange factor
what does GEF control
removal of GDP and its replacement by GTP; protein that activates pathways
what does GEF do
binds onto inactive G protein and removes GDP and replaces it w/ GTP
what would happen if no GEF
would never become activated
what are G proteins known as
GTPase
what can GTPase do
self timer to turn itself off, but it’s slow
why dow e need second regulator protein to turn it off
inactivating GAP protein will bind to GTPase, accelerates timer
what are GAPs
GTPase Activating Protein
what is being activated in GAPs
intrinsic GTPase activity (so it can turn itself off quicker)
how can multiple proteins find each other in hella crowded env.? and quickly?
proteins pre-positioned at right place by scaffold proteins so they are where they need to be at the right time
describe scaffolding in receptor tyrosine kinases
receptor acts as scaffold; when RTKs phosphorylate each other, creates scaffold or docking sites where
what does scaffolding require
specific protein domains to mediate
positive feedback
when B is activated, it binds and activates more copies of A
what DONT you need when B is activated
initial signal molecule
negative feedback
A activates B signaling protein, B binds and inhibits A
what happens when pathway turns on
tries to turn itself back off
pos feedback in kinase
when upstream signal kinase is activated, binds and phosphorylates substrate E (inactive kinase); goes and feedbacks on earlier step on pathway
what happens as long as signal is present in pos
pathway is activated
what happens if signal is gone in pos
pathway still on; but need initial molecule at some point
what happens when kinase E is activated thru phosphorylation thru upstream kinase
phosphorylates an inhibitor that deactivates E
how do cells adjust sensitivity to a signal
negative feedback (turns itself off), receptor inactivation (G proteins and natty timer)
how are cell dynamics controlled
intracellular signaling
how do receptors work
receive signal, transmit it into cell thru signal transduction pathways
what governs signal transmission + effects
proteins and post-translational modification
how are signals modulated
pos and neg feedback; inhibited
