Chapter 16: Cell Signaling Flashcards
1
Q
What is signal transduction
A
process of converting one type of signal to another
2
Q
What are agonist?
A
Signal molecules that activates receptors
3
Q
What are antagonist?
A
Signal molecules that block receptor activity
4
Q
How are signal molecule detected by a target cell?
A
Receptor proteins (receptors)
5
Q
What are the 5 types of cell communication
A
- Endocrine
- Paracrine
- Synaptic
- Contact-Dependent
- Autocrine
6
Q
What is long distance, wide distribution cell communication?
A
Signal sent over long distance throughout the whole body
7
Q
What type of communication uses with long distance wide distribution
A
Endocrine
8
Q
What are the signaling molecules associated with long distance wide distribution?
A
Hormones
9
Q
What does hormones do?
A
Extracellular signaling molecules that mediate endocrine signaling made by endocrine cells
Ex: Insulin
10
Q
What type of communication uses short distance, local distribution
A
- Paracrine
- Autocrine
11
Q
What is short distance local distribution
A
Signal molecules diffuse locally instead of going into the blood streams
12
Q
What signaling molecule carry out short distance local distribution
A
- Local mediator
- Autocrine signaling
13
Q
What is local mediator?
A
Extracellular signaling molecules that mediate paracrine signaling
14
Q
What is autocrine signaling?
A
Type of autocrine signaling in which cells responds to local mediator that they themselves produce
15
Q
What is the difference between endocrine and paracrine/autocrine signaling
A
The distance
Paracrine: signal spread and lifetime will be shorter, which affects the local area
Endocrine: signal spread over the whole body
16
Q
What is synaptic communication?
A
A long distance, cell specific communication in which message is delivered over long distance, but to a specific recipients not widely like hormones
17
Q
What type of communication uses long distance cell specific
A
Synaptic
18
Q
What contributes to long distance cell specific communication
A
- Synapse
- Neurotranmitter
19
Q
What is a synpase?
A
junction between axon of one neuron and dendrites of another neuron where information is transferred
20
Q
What are neurotransmitters?
A
Signaling molecules released from axons at the synapse
21
Q
What type of communication uses cell-cell specific
A
Contact Dependent
22
Q
What is contact dependent communication?
A
A cell-cell specific communication in which membrane bound signal molecules bind to membrane receptors
23
Q
How does contact dependent communication work?
A
Cell make direct physical contact to the target cell’s receptors
Delta and Notch
24
Q
If cells are exposed to multiple signaling molecule, How do they know which signal to respond?
A
Each cell respond to a limited set because their receptor is specific, thus production of limited set of receptor allow a cell to restrict the numbers of signal that can affect it
25
Where are the two location receptors can be located on the cell?
1. On the cell's surface (cell surface)
2. In the cell (intracellular)
26
What determines the response of the cell to a particular signal?
A cell's intracellular relay system
27
How is it possible that the same signal can evoke different response?
Cells have different type of receptors/ intracellular relay proteins
28
Why is combinatorial control so crucial to cell?
Cell needs a combination of signal molecule for it to regulate the cell's behavior. If the cell is deprived from its necessary signal, it will undergo apoptosis
29
What are the 5 components of intracellular signaling pathway
1. Relay the signal onward
2. Amplify the signal
3. Integrate more than one
extracellular signal
4. Distribute the signal to more
than one effector protein
5. Modulate the response by
feedback
30
How can intracellular signaling protein act as molecular switches?
Positive Feedback and Negative Feedback
31
What are the two main molecular switches that regulate signaling cascade?
1. Protein Phosphorylation
2. GTP binding protein
32
Describe protein phosphorylation
Attaching a phosphate group to an amino acid: serine, theronine, or tyrosine using kinase and dephosphorylation using phosphatase, stimulating or inhibiting protein activity
33
What is the result of protein phosphorylation
Phosphorylation cascade: Because protein switch can act as kinase, one kinase can phosphorylates the next kinase in the sequence, and so on, transmitting the signal onward and, in the process, amplifying, distributing, and regulating it
34
What are the three amino acids that are phosphorylated
Serine/Threonine and Tyrosine
35
Describe GTP binding protein
A protein bind to GTP will be activated while protein bind to GDP will be inactivated
36
What are the proteins that add/remove GTP
Guanine nucleotide Exchange Factor (GEF)
GTPase activating protein (GAP)
37
What does GEF do?
promote exchange from GDP to GTP, activating the protein
38
What does GAP do
Promote GTP hydrolysis, deactivating the protein
39
What is receptor down regulation
decrease in total receptor number in the cell
40
What causes receptor down regulation
1.ligand binds to receptor
2. ligand/ receptor complex is endocytosed
3. after chronic receptor stimulation, receptor
levels fall, resulting in desensitization; degration of receptor from overused by agonist
41
What are the three type of cell surface receptors?
1. Ion channel coupled receptors
2. G Protein coupled receptor
3. Enzyme coupled receptor
42
What is ion channel coupled receptors
Receptors, in the form of gated ion channel, that convert a chemical signal into an electrical signal
43
What is G protein coupled receptors (GPCR)
7 transmembrane domains receptors in eukaryotes.
44
What does GPCR do?
Mediate responses to a diverse signals hormones, local mediators, neurotransmitters
45
What happens when an extracellular signal bind to GPCR
It undergoes a conformational change that enables it to activate a G protein
46
How does G Protein get activated and what happens when it activates
G protein are activated whenever an extracellular signal bind to GPCR. This caused the α subunit to be less affinitive for GDP, exchanging the molecule for GTP, activating it.
47
Describe the structure of G protein
There are alpha, beta, and gamma subunit, in which the alpha and gama subunit is tethered to the membrane by lipid tails.
48
What are the member of G alpha protein
G alpha S
G alpha I
G alpha q
49
What happens when G alpha S is activated
Stimulation of adenylyl cyclase
50
What happens when G alpha I is activated
Inhibition of adenylyl cyclase
51
What happens when G alpha q is activated?
stimulates release of calcium from intracellular store,
52
What is the trimeric G protein
G protein that has alpha, β,γ subunit
53
Describe the process whenever GPCR is activated
1. Ligand binds to GPCR, causing a conformational change that allow interaction with the trimeric-G-protein
2. The alteration ofthe α subunit of the G protein allows it to exchange its GDP for GTP.
3. G protein alpha subunit dissociate with the G protein βγ subunit because of the conformational change
4. Signal transduction ends when Gα hydrolyzes its GTP, becomes GDP bound and reassociates with Gβγ
54
How is G protein inactivated
GTP hydrolysis by G alpha subunit hydrolyzing its GTP so it can reassociate with the βγ unit
55
How does the alpha subunit of G protein reassociate with its beta/gamma subunit?
It can hydrolyze its own GTP, deactivating it so it can reassociated
56
How can some G protein activate ion channel?
1.. Acetylcholine binds to GPCR
2. G protein is activated and alpha subunit separate from βγ subunit.
3. βγ subunit open K+ channel by increasing its permeability to K+.
Inactivated of αlpha subunit by hydrolysis of its bound GTP returns G protein to its original state, allowing K+ to close.
57
How can G protein trigger the synthesis or release of second messenger molecule?
Activation of G α subunit caused the Gαs to be stimulated, causing a stimulation of adenylyl cyclase, producing cyclic AMP,
and phospholipase C which produce inositol trisphosphate and diacylglycerol, ultimately producing Ca 2+
Activation of G alpha a - > adenylyl cyclase -> cyclic AMP binds to PKA
Activation of G alpha q -> P3/DAG -> Ca 2+
58
What is the primary target of cyclic AMP?
Protein Kinase A (pka)
59
Describe the pathway that shows how glycogen breakdown is activated
1. Epinephrine binds to GPCR
2. G alpha s is activates
3. Adenylyl Cyclase is produced
4. cAMP is produced
5. cAMP binds to pka
6. pKA phosphorylation promote glycogen breakdown
60
Describe the pathway that shows how transcription of proteins involved in learning is activated
1. cAMP binds to PKA
2. PKA enter nucleus
3. PKA phosphorylate transcription regulator
4. Target gene is transcribed
61
What happens when signaling molecule acts through Gαq?
Phospholipase C is activated instead of adenylyl cyclase.
62
What does phospholipase C do?
cleaves an inositol phospholipid that is embedded in the
cytoplasmic face of the plasma membrane to generate two second-messenger
molecules: IP3 and DAG
63
What are the two molecules that results from the cleavage of inositol phospholipid?
Inositol trisphosphate (IP3)- diffuse in cytosol
Diacylglycerol (DAG)- remain in membrane
64
What does IP3 do after its production?
binds to and opens calcium channels in the ER
65
What happens to Diacylglycero after its production
remains embedded in the plasma membrane and help recruit and activate PKC alongside with calcium
66
How is protein kinase C (PKC) activated?
By the DAG that is on the membrane and the calcium that were release from IP3 opening the channel
67
How can calcium serve as a second messenger molecule?
1. stimulates cell responses by binding to and
influencing Ca2+ binding protein
2. activates NOS to generate NO and cGMP
signaling to dilate blood vessels
68
What happens when calcium binds to calmodulin?
Calmodulin undergoes a conformational change that allows it to bind it
Ca2+/calmodulin-dependent protein
kinase (CaM-kinase)
69
What can CaM-Kinase do after its production?
It can bind to Ca2+/calmodulin-dependent protein
kinase (CaM-kinase) , which can phosphorylate its target
Ex: important part in some forms of learning and
memory in mammalian brain
70
What happens when Calcium activates Nitric Oxide Synthase (NOS)?
Nitric Oxide (NO) and cyclic GMP (cGMP) is generated signaling to dilate blood vessels
NO binds to guanylyl cyclase to make cGMP
71
Describe the process of how muscle is relaxed in the cell wall
1. neurotransmitter acetylcholine causes the blood vessel to dilate by binding to a GPCR
2. G protein, Gq, is activated
3. Calcium is released from the opening of ion gated channel from the beta-gamma subuit
4. Ca2+ activates nitric oxide synthase (NOS), stimulating the production of NO
5. NO then diffuses out of the endothelial cells, causing muscle cell to relax
72
Give an example on how intracellular signaling can adapt or amplify a signal
response of the eye to light
1. light is sensed by rhodopsin, a G-protein-coupled light receptor.
2. Rhodopsin activates a G protein called transducin.
3. Transducin activates a signaling cascade
4. Signaling cascade causes cation channels to close producing change in membrane potential and altered neurotransmitter release
5. Signal is relayed to brain
73
Why do cells have evolved intracellular calcium store for signaling even though there is abundant extracellular calcium.
The rapid clearing of Ca2+ ions from the cytosol by Ca2+ pumps prevents Ca2+ from diffusing any significant distance in the cytosol.
74
Contrast enzyme couple receptor and GCPR
GPCR associate with G protein. Cytoplasmic domain acts as an enzyme or form a complex with another protein that acts as an enzyme
75
Describe the activation of process of enzyme couple receptors
1. Binding of signal causes two Receptor tyrosine kinases (RTK) receptors to dimerize – leading to enzyme activation
2. The two intracellular tails of the receptors come together, activating their kinase domain
3. The tails phosphorylate together and the tails serves as docking sites
4. RTKs transmit signals simultaneously to multiple destinations, causing activation of downstream signaling pathway
76
How does the RTK return to its inactive state?
1. tyrosine phosphatases remove the phosphates that were added
2. RTK undergo endocytosis and are destroyed by lysosome
77
What is ras?
a small GTP-binding protein that is activated by RTK
78
What happens after ras is activated?
RTK is phosphorylated and recruits Ras GEF
1. GEF activates MAP kinase kinase kinase
2. MAP kinase kinase kinase activates MAP kinase kinase
3. MAP kinase kinase activates MAP kinase
4. Changes in protein activity and gene expression
79
What are the two consequences of activation of RTK
1. Ras Activation
2. PI3 Activation
80
What happens when PI3 is activated?
Promote membrane docking and activates AKT
81
What is AKT and what does it do
Protein kinase B
promotes growth and survival of cell type by inactivating the signaling proteins it phosphorylates.
1. Inactivate Bad
2. Activate Tor
82
What does AKT inactivate
Bad - an apoptosis promoter
83
What does AKT activate
Tor - a protein that stimulates cell growth
by inhibiting protein degradation and stimulating
protein synthesis
84
Describe the process that leads to AKT promoting cell growth
1. RTK is activated
2. IP3 is activated
3. IP3 sends signal to AKT
4. AKT phosphorylate Bad and Activate Tor
Bcl2 inhibits apoptosis and Tor inhibits protein degration
85
What is notch?
receptor that controls the development of neural cells in Drosophila
86
What happens when notch binds to delta?
the notch receptor is cleaved releasing the cytosolic tail of the receptor, which is then free to move to the nucleus, where it helps to activate the appropriate set of Notch-responsive genes
87
What are the two ways signaling molecule can cross the plasma membrane?
1. Direct activation of an intracellular enzyme.
2. Bind to intracellular receptors.
88
How does steroid hormones cross the plasma membrane?
uses Intracellular receptors
1. Nuclear receptor binds to steroid hormones
2. receptor-cortisol complex move into nucleus
3. complex binds to regulatory region of target gene to activate transcription
89
Compare and Contrast plant and mammalian signaling
Plant cells don’t use RTKs, steroid-hormone type nuclear
receptors, cAMP, and have few GPCRs. They use ethylene instead to regulate their function
90
Describe the process that leads to AKT promoting cell growth
1. AKT phosphorylate Bad
2. This release Bcl2 from Bad
3. Bcl2 leads to cell survival by inhibition of apoptosis
