2.7: Concepts in Cell Signalling Flashcards

1
Q

cell signalling allows cells to:

A
  • sense and respond to their environment
  • communicate with each other
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2
Q

define extracellular signalling molecules

A

any molecule that can transmit signals between cells (ions, hormones, proteins, gases, ligands)

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3
Q

define receptor and ligand

A

receptor: binds a signalling molecule
ligand: a signaling molecule that can be bound by a receptor

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4
Q

define intracellular signaling molecule

A

any molecule that can transmit a signal within a cell (ions metabolites proteins)

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5
Q

can extracellular signaling molecules go inside the cell

A

yes, sometimes, as long as they transmit signals between cells

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6
Q

define secondary messengers and give 2 examples

A

non-protein small intracellular signalling molecules - ions, metabolites

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7
Q

are secondary messengers classified as ec or ic signaling molecules

A

ic

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8
Q

define effectors

A

receive signals to change cell behaviour

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9
Q

t/f extracellular signaling molecules can act over both short and long distances

A

yes

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10
Q

explain the mechanisms for how extracellular signaling molecules can act over short distances

A

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

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11
Q

distinguish between paracrine and autocrine

A

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

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12
Q

list what signal movement is restricted by in autocrine and paracrine signaling

A
  • internalization by cells (gobble)
  • degradation or destruction
  • limited diffusion distance
  • receptor expression
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13
Q

describe the mechanisms for how extracellular signaling molecules can act over long distances

A

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

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14
Q

in order to receive the signal, what must the target cell express

A

the target cell must express the receptor protein to be able to receive the signal. the ligang binding activates the receptor

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15
Q

t/f extracellular signaling molecules can go to intracellular receptors (ie in nucleus, cytosol, wtv)

A

yes

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16
Q

many signaling pathway components act like molecular switches, signaling usually involves rapid and reversible changes to proteins such as:

A
  • different protein interactions
  • increase/decrease in enzyme activity
  • changes in subcellular localization
  • protein synthesis or degradation
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17
Q

signaling usually involves rapid and reversible changes to proteins, these changes are achieved by common molecular mechanisms: (4)

A
  • phosphorylation
  • gtp binding
  • ubiquitination
  • other small molecule binding
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18
Q

in order for signaling pathways to be efficient when on, they must be…

A

turned off

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19
Q

describe how intracellular signals can be transmitted via protein phosphorylation

A
  • 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
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20
Q

what is the most common way intracellular signals can be transmitted

A

protein phosphorylation

21
Q

list and state the function of relevant enzymes in protein phosphorylation

A
  • protein kinase adds a phosphate group
  • protein phosphatases removes a phosphate group
22
Q

describe how intracellular signals can be transmitted via gtp binding proteins

A

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

23
Q

list and state the function of relevant enzymes in intracellular signaling transmission via gtp binding proteins

A

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

24
Q

describe how intracellular signals can be transmitted via protein ubiquitination

A
  • 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
25
Q

t/f are secondary messengers proteins

A

no

26
Q

intracellular signals can be transmitted via small molecules, these are typically produced in large amounts to amplify the signal, provide some examples

A
  • cyclic AMP
  • ca2+
  • diacylglycerol (DAG) lipid
  • inositol triphosphate (IP3)
27
Q

Which of the following is most likely to inhibit signaling?
a) GEF activator
b) Phosphatase inhibitor
c) GAP inhibitors
d) Kinase inhibitors

A

D.
A activates, B blocks removal of phosphate, C blocks the blocker

28
Q

which one is faster, synaptic or endocrine signaling and why

A

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)

29
Q

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

A
  1. slow
  2. fast
  3. extremely fast
30
Q

_________ steps are important parts of signaling pathways

A

inhibitory

31
Q

feedback creates a loop in the signaling pathway, without feedback what would happen to the pathway

A

the pathway would only be “on” when the signal is present

32
Q

which type of feedback can create an “all or none” switch

A

positive feedback

33
Q

describe the result of positive feedback creating an all or none switch

A

stimulus activates A, A activates B, B activates more A (feedback loop)

output intensity is increased, output can continue even after stimulus is removed

34
Q

describe the patterns that can be created by negative feedback

A

long delay: creates an oscillating output
short delay: output intensity is decreased (adaptation or desensitization) - like an alarm clock
ALWAYS A DELAY

35
Q

list the 5 mechanisms possible to achieve negative feedback

A
  1. regular negative feedback
  2. delayed feed forward
  3. receptor inactivation, but some output is passed through
  4. receptor sequestration - receptor gets taken by endosome w the ligand and endosome puts receptor back after
  5. receptor destruction - in lysosome
36
Q

t/f cells can receive multiple signals at once

A

yes, cell survival often requires specific signals and additional signals can be required for growth, division, and differentiation (you can tell through coincidence detectors)

37
Q

state the way that signals can be specific in a complex cellular environment

A

signaling complexes, coincidence detectors

38
Q

signaling complexes can be organized on scaffold proteins, explain what these are

A

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.

39
Q

scaffold proteins bind which kind of signaling molecules

A

intracellular signaling proteins

40
Q

t/f some signaling complexes can still be organized on scaffold proteins ever without a signal

A

yes, not all

41
Q

describe how scaffold protein complexes are assembled once signaling is activated

A
  • perception of the signal modifies the receptor (phosphorylation)
  • ic signaling molecules bind to these modifications
  • complex is assembled only when the signal is present
42
Q

____________ can help scaffold signaling proteins and ___________ help signaling complexes assemble

A

phosphoinositides (PIPs), protein interaction domains

43
Q

how can phosphoinositides (PIPs) help scaffold signaling proteins

A

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)

44
Q

an example of a protein interaction domain is a SH3, is it t/f that diff SH3 domains bind to diff prot sequnces

A

yes, but there is always specificity. domains are mixed and matched in different proteins

45
Q

list all the protein interaction domains and what they bind to

A
  1. SH3 domains bind to proline rich sequences
  2. SH2 & PTB domains bind to phosphorylated tyrosines
  3. PH domains bind phosphoinositides
46
Q

SH2 and PTB domains bind phosphorylated tyrosines, how do these maintain the specificity

A

the domains will recognize the neighbours to have the specificity

47
Q

which protein interaction domains do not require phosphorylation? which proteins interact only when the receptor is phosphorylated?

A

protein interaction domains do not require phosphorylation: SH3 or other domains
proteins interact only when the receptor is phosphorylated: SH2 and PTB domains

48
Q

coincidence detectors require one/multiple signals

A

multuple

49
Q

describe how coincidence detectors work

A
  • 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