2.7: Concepts in Cell Signalling

Question 1

cell signalling allows cells to:

Answer 1

• sense and respond to their environment
• communicate with each other

Question 2

define extracellular signalling molecules

Answer 2

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

Question 3

define receptor and ligand

Answer 3

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

Question 4

define intracellular signaling molecule

Answer 4

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

Question 5

can extracellular signaling molecules go inside the cell

Answer 5

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

Question 6

define secondary messengers and give 2 examples

Answer 6

non-protein small intracellular signalling molecules - ions, metabolites

Question 7

are secondary messengers classified as ec or ic signaling molecules

Answer 7

ic

Question 8

define effectors

Answer 8

receive signals to change cell behaviour

Question 9

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

Answer 9

yes

Question 10

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

Answer 10

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

Question 11

distinguish between paracrine and autocrine

Answer 11

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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

yes

Question 16

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

Answer 16

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

Question 17

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

Answer 17

• phosphorylation
• gtp binding
• ubiquitination
• other small molecule binding

Question 18

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

Answer 18

turned off

Question 19

describe how intracellular signals can be transmitted via protein phosphorylation

Answer 19

• 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

Question 20

what is the most common way intracellular signals can be transmitted

Answer 20

protein phosphorylation

Question 21

list and state the function of relevant enzymes in protein phosphorylation

Answer 21

• protein kinase adds a phosphate group
• protein phosphatases removes a phosphate group

Question 22

describe how intracellular signals can be transmitted via gtp binding proteins

Answer 22

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

Question 23

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

Answer 23

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

Question 24

describe how intracellular signals can be transmitted via protein ubiquitination

Answer 24

• 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

Question 25

t/f are secondary messengers proteins

Answer 25

no

Question 26

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

Answer 26

- cyclic AMP - ca2+ - diacylglycerol (DAG) lipid - inositol triphosphate (IP3)

Question 27

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

Answer 27

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

Question 28

which one is faster, synaptic or endocrine signaling and why

Answer 28

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)

Question 29

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

Answer 29

1. slow 2. fast 3. extremely fast

Question 30

_________ steps are important parts of signaling pathways

Answer 30

inhibitory

Question 31

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

Answer 31

the pathway would only be "on" when the signal is present

Question 32

which type of feedback can create an "all or none" switch

Answer 32

positive feedback

Question 33

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

Answer 33

stimulus activates A, A activates B, B activates more A (feedback loop) output intensity is increased, output can continue even after stimulus is removed

Question 34

describe the patterns that can be created by negative feedback

Answer 34

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

Question 35

list the 5 mechanisms possible to achieve negative feedback

Answer 35

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

Question 36

t/f cells can receive multiple signals at once

Answer 36

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

Question 37

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

Answer 37

signaling complexes, coincidence detectors

Question 38

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

Answer 38

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.

Question 39

scaffold proteins bind which kind of signaling molecules

Answer 39

intracellular signaling proteins

Question 40

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

Answer 40

yes, not all

Question 41

describe how scaffold protein complexes are assembled once signaling is activated

Answer 41

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

Question 42

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

Answer 42

phosphoinositides (PIPs), protein interaction domains

Question 43

how can phosphoinositides (PIPs) help scaffold signaling proteins

Answer 43

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)

Question 44

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

Answer 44

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

Question 45

list all the protein interaction domains and what they bind to

Answer 45

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

Question 46

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

Answer 46

the domains will recognize the neighbours to have the specificity

Question 47

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

Answer 47

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

Question 48

coincidence detectors require one/multiple signals

Answer 48

multuple

Question 49

describe how coincidence detectors work

Answer 49

- 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