2.7: Concepts in Cell Signalling Flashcards
cell signalling allows cells to:
- sense and respond to their environment
- communicate with each other
define extracellular signalling molecules
any molecule that can transmit signals between cells (ions, hormones, proteins, gases, ligands)
define receptor and ligand
receptor: binds a signalling molecule
ligand: a signaling molecule that can be bound by a receptor
define intracellular signaling molecule
any molecule that can transmit a signal within a cell (ions metabolites proteins)
can extracellular signaling molecules go inside the cell
yes, sometimes, as long as they transmit signals between cells
define secondary messengers and give 2 examples
non-protein small intracellular signalling molecules - ions, metabolites
are secondary messengers classified as ec or ic signaling molecules
ic
define effectors
receive signals to change cell behaviour
t/f extracellular signaling molecules can act over both short and long distances
yes
explain the mechanisms for how extracellular signaling molecules can act over short distances
contact dependent: two cells must be very close to connect membrane-bound signal in signaling cell to membrane-bound receptor in target cells
paracrine: signaling cell releases a local diffusible signal to target cells
autocrine: a cell secretes a diffusible signal for itself
distinguish between paracrine and autocrine
paracrine: signaling cell releases a local diffusible signal to target cells
autocrine: a cell secretes a diffusible signal for itself
*para to others, auto it itself
list what signal movement is restricted by in autocrine and paracrine signaling
- internalization by cells (gobble)
- degradation or destruction
- limited diffusion distance
- receptor expression
describe the mechanisms for how extracellular signaling molecules can act over long distances
synaptic: neuron extends an axon to reach (and make close contact with) a distance target cell (the synapse is short but the distance from neuron is long)
endocrine: endocrine cell secretes hormones into the bloodstream for long range distribution in the body
in order to receive the signal, what must the target cell express
the target cell must express the receptor protein to be able to receive the signal. the ligang binding activates the receptor
t/f extracellular signaling molecules can go to intracellular receptors (ie in nucleus, cytosol, wtv)
yes
many signaling pathway components act like molecular switches, signaling usually involves rapid and reversible changes to proteins such as:
- different protein interactions
- increase/decrease in enzyme activity
- changes in subcellular localization
- protein synthesis or degradation
signaling usually involves rapid and reversible changes to proteins, these changes are achieved by common molecular mechanisms: (4)
- phosphorylation
- gtp binding
- ubiquitination
- other small molecule binding
in order for signaling pathways to be efficient when on, they must be…
turned off
describe how intracellular signals can be transmitted via protein phosphorylation
- protein kinase adds a phosphate group and phosphatases removes it
- phosphorylation can change protein structure or charge
- this can affect protein activity, interactions, or localization
- phosphorylation usually turns a protein or signaling pathway on BUT EXCEPTIONS
what is the most common way intracellular signals can be transmitted
protein phosphorylation
list and state the function of relevant enzymes in protein phosphorylation
- protein kinase adds a phosphate group
- protein phosphatases removes a phosphate group
describe how intracellular signals can be transmitted via gtp binding proteins
gefs (guanine nucleotide exchange factors) helps to exchange gdp to gtp
gaps (gtpase-activating proteins) helps to activate the gtpase activity to hydrolyze gtp to gdp
gtp binding can affect protein activity, interactions, or localization. gtp binding usually turns a protein/signaling pathway on
list and state the function of relevant enzymes in intracellular signaling transmission via gtp binding proteins
gefs (guanine nucleotide exchange factors) helps to exchange gdp to gtp
gaps (gtpase-activating proteins) helps to activate the gtpase activity to hydrolyze gtp to gdp
*gaps probs turns the protein off
describe how intracellular signals can be transmitted via protein ubiquitination
- e1,e2,e3 ligases help to activate the small protein ubiquitin and attach it to the target protein
- ubiquitination can change protein activity, localization, stability
- multiubiquitylation: endocytosis
- polyubiquitylation on lys48: proteasomal degradation
t/f are secondary messengers proteins
no
intracellular signals can be transmitted via small molecules, these are typically produced in large amounts to amplify the signal, provide some examples
- cyclic AMP
- ca2+
- diacylglycerol (DAG) lipid
- inositol triphosphate (IP3)
Which of the following is most likely to inhibit signaling?
a) GEF activator
b) Phosphatase inhibitor
c) GAP inhibitors
d) Kinase inhibitors
D.
A activates, B blocks removal of phosphate, C blocks the blocker
which one is faster, synaptic or endocrine signaling and why
synaptic is very fast (fraction of a second) vs endocrine is slow bc it requires blood circulation to distribute the signaling molecule (minutes or longer)
state whether the following changes are fast or slow:
1. changes to transcriptions and translation
2. changes to protein function
3. changes in membrane potential
*some ic pathway signalling can be both fast and slow
- slow
- fast
- extremely fast
_________ steps are important parts of signaling pathways
inhibitory
feedback creates a loop in the signaling pathway, without feedback what would happen to the pathway
the pathway would only be “on” when the signal is present
which type of feedback can create an “all or none” switch
positive feedback
describe the result of positive feedback creating an all or none switch
stimulus activates A, A activates B, B activates more A (feedback loop)
output intensity is increased, output can continue even after stimulus is removed
describe the patterns that can be created by negative feedback
long delay: creates an oscillating output
short delay: output intensity is decreased (adaptation or desensitization) - like an alarm clock
ALWAYS A DELAY
list the 5 mechanisms possible to achieve negative feedback
- regular negative feedback
- delayed feed forward
- receptor inactivation, but some output is passed through
- receptor sequestration - receptor gets taken by endosome w the ligand and endosome puts receptor back after
- receptor destruction - in lysosome
t/f cells can receive multiple signals at once
yes, cell survival often requires specific signals and additional signals can be required for growth, division, and differentiation (you can tell through coincidence detectors)
state the way that signals can be specific in a complex cellular environment
signaling complexes, coincidence detectors
signaling complexes can be organized on scaffold proteins, explain what these are
scaffold proteins bind ic signaling proteins. scaffolds can: limit protein movement, ensure signals are passed in correct order. complex is assembled even if there is no signal.
scaffold proteins bind which kind of signaling molecules
intracellular signaling proteins
t/f some signaling complexes can still be organized on scaffold proteins ever without a signal
yes, not all
describe how scaffold protein complexes are assembled once signaling is activated
- perception of the signal modifies the receptor (phosphorylation)
- ic signaling molecules bind to these modifications
- complex is assembled only when the signal is present
____________ can help scaffold signaling proteins and ___________ help signaling complexes assemble
phosphoinositides (PIPs), protein interaction domains
how can phosphoinositides (PIPs) help scaffold signaling proteins
perception of the signal modifies the membrane lipids (phosphorylation of phosphoinositides). ic signaling molecules bind to the new PIPs.
(the membrane bound PIPs can be hyperphosphorylated when the signal molecule activates the receptor so they can activate ic signaling proteins to cause a downstream cascade)
an example of a protein interaction domain is a SH3, is it t/f that diff SH3 domains bind to diff prot sequnces
yes, but there is always specificity. domains are mixed and matched in different proteins
list all the protein interaction domains and what they bind to
- SH3 domains bind to proline rich sequences
- SH2 & PTB domains bind to phosphorylated tyrosines
- PH domains bind phosphoinositides
SH2 and PTB domains bind phosphorylated tyrosines, how do these maintain the specificity
the domains will recognize the neighbours to have the specificity
which protein interaction domains do not require phosphorylation? which proteins interact only when the receptor is phosphorylated?
protein interaction domains do not require phosphorylation: SH3 or other domains
proteins interact only when the receptor is phosphorylated: SH2 and PTB domains
coincidence detectors require one/multiple signals
multuple
describe how coincidence detectors work
- protein Y can be phosphorylated in 2 places
- A or B alone can only trigger one phosphorylation site on Y
- Y is only active if it has received both phosphorylation therefore Y is a coincidence detector for pathways A and B
