Ch. 16 Principles of Cell Signaling

Question 1

list ways cells can respond to their environments

Answer 1

• cell movement
• shape
• metabolism
• gene expression

Question 2

what is the purpose of cellular communication, particularly for multicellular organisms

Answer 2

• reflexes
• behaviours
• development
• survival

Question 3

briefly describe the pathway of cells sending signals

Answer 3

signal cell sends signal molecules which binds to extracellular receptor on target cell and creates a response

Question 4

list the stages of cell signaling

Answer 4

1. reception
2. transduction
3. response

Question 5

describe the reception stage of cell signalling

Answer 5

• target cells sense signal molecule is coming their way
• signal molecule (=ligand) binds to cellular receptor protein either on or inside cell

Question 6

describe the transduction stage of cell signaling

Answer 6

• binding causes conformational shape change for activation
• signal is converted into a form that will generate a response –> multiple = signal transduction pathway by relay molecules

Question 7

describe response stage of cell signaling

Answer 7

• cellular activity results from transduced signal (i.e. catalysis, rearrangement of cytoskeleton, gene activation)

Question 8

draw out endocrine signaling

Answer 8

• main point: thru bloodstream

Question 9

draw out paracrine signaling

Answer 9

main point: direct & close

Question 10

draw out neuronal signaling

Answer 10

main point: NT, axon, synapse present

Question 11

draw out contact-dependent signaling

Answer 11

main point: membrane-bound signal molecule attaches onto receptor of target cell

Question 12

cell specialization is an important mechanism for many organisms. how does it work? use fruit flies as ex.

Answer 12

• multicellular organisms don’t need to rely on one cell for survival which allows the cells to have same general properties but differentiate in roles
• in fruit flies one cell in centre of unspecified epithelial cells will turn into a neuron
• the cells around the neurons will differentiate into non-neuronal cells

Question 13

how do cells decide what signals to respond to

Answer 13

dynamic receptor protein expression (few receptors to begin with, some of these inactivate, internalize, degrade, etc.)

Question 14

draw out response of heart muscle, salivary gland, and skeletal muscle cells due to their signal molecules

Answer 14

main points: hmc = lower heart rate and force of contraction

sgc = secretion

smc = contraction

Question 15

a cell’s response to a signal can be fast or slow. how can we immediately know is the response is slow

Answer 15

when transcription/translation needed

Question 16

draw out the flow for main steps in fast and slow cell response to signal

Answer 16

…

Question 17

draw out the dif b/w cell surface and intracellular receptors

Answer 17

….

Question 18

steroid hormones are able to activate gene transcription. draw out this slow pathway showing steroid hormone outside cell reaching nucleus with main steps

Answer 18

….

Question 19

what are the main classes of cell-surface receptors

Answer 19

• ion channel-coupled
• G-protein coupled
• enzyme-coupled

Question 20

some intracellular signaling proteins are able to act as molecular switches (can turn ON/OFF). draw the cycles of how signaling by protein phosphorylation and by GTP-binding protein can occur

Answer 20

…

Question 21

describe intracellular signaling pathways of extracelullar signals. draw out the pathway with main steps

Answer 21

• simple path to target
• has amplification step to inc response efficacy
• signal can be distributed to dif target pathways

Question 22

describe GPCRs

Answer 22

• biggest family of cell surface receptors
• evolutionarily ancient
• similar core structures
• different functions
• membrane associated
• activators for G proteins

Question 23

what are the subunits for G proteins

Answer 23

α, β, γ

Question 24

draw out how GPCRs activate G proteins

Answer 24

main points: resting state with GDP; receptor activates with signal molecule and GDP dissociation; GTP binds to α for effector activation

Question 25

draw out how target proteins are activated by G proteins

Answer 25

main points: GTP x α bound activated subunit attaches to target protein which causes GTP hydrolysis into GDP +P inactive α subunit attaches to activated β γ complex making inactive G protein

Question 26

why are on/off molecular swtiches important

Answer 26

- don't always want a response - EX no off switch w cholera toxin leads to diarrhea and cause cause death in extreme situations

Question 27

draw out how heart rate regulation occurs with G proteins and K+ channels

Answer 27

main points: acetylcholine binds to GPCR activating K+ channel K+ exits and G protein inactivates by hydrolysis which makes channel close inactive α subunit attaches to activated β γ complex making inactive G protein

Question 28

what type of effect does K+ have on heart muscle

Answer 28

- inhibitory - prevents heart from contracting as fast

Question 29

adenylyl cyclase is able to catalyze

Answer 29

cAMP synthesis

Question 30

phospholipase C (PLC) is able to catalyze

Answer 30

IP3 and DAG synthesis

Question 31

how can Ca+2 be an important intracellular messenger

Answer 31

- neurotransmission - contraction - secretion - fertilization

Question 32

draw out how G protein activation leads to phospholipase c activation and further leads to IP3 and DAG synthesis

Answer 32

main points: signal molecule activates GPCR; activated g protein leads to activated phos. lip. c making inositol phospholipid; this splits into DAG (diaglycerol) and IP3. IP3 opens Ca+2 channel to let Ca+2 ions from ER lumen go to (cytosol) PKC and DAG also attaches to PKC causing activation

Question 33

how is Ca+2 able to mediate cell responses

Answer 33

Ca+2 entering the cytosol is able to interact with Ca+2 responsive proteins

Question 34

what is the most common Ca+2 responsive protein

Answer 34

calmodulin (main intracellular receptor)

Question 35

how does Ca+2 affect calmodulin

Answer 35

- binding leads to conformational shape change - calmodulin wraps around the target protein/kinase and causes activation - an example of this is calmodulin-dependent protein kinases which cannot activate

Question 36

what is the largest class of enzyme-coupled receptors

Answer 36

receptor tyrosine kinases (RTKs)

Question 37

what are enzyme-coupled receptors

Answer 37

- single transmembrane proteins with extracellular ligand binding domain - have enzymatic activity themselves

Question 38

what are intracellular domains capable of acting; doing

Answer 38

- enzyme; - forming a complex with another protein that acts as an enzyme

Question 39

define dimerization

Answer 39

two signal molecules that are able to bring 2 receptors together through bonding

Question 40

draw out how RTKS are activated by dimerization

Answer 40

....

Question 41

what does RTK activation by dimerization

Answer 41

complex of proteins bound to phosphorylated tyrosines

Question 42

why are phosphates important in activation of downstream intracellular signaling pathways

Answer 42

phosphates are able to recruit proteins that propagate signals further

Question 43

most RTKs are able to activate the what protein

Answer 43

monomeric GTP-binding protein Ras

Question 44

describe the Ras protein

Answer 44

- molecular switch - intrinsic GTPase activity

Question 45

draw out how Ras is able to be activated

Answer 45

...

Question 46

what results can activation of MAP-kinase signaling molecules lead to

Answer 46

changes in protein activity and gene expression

Question 47

what happens if the Ras protein has a mutation

Answer 47

- mutation interferes w/ GTPase activity, which prevents Ras from turning off (~30% of human cancers) - GTP cannot hydrolyze