Unit 3 Flashcards
(104 cards)
1
Q
What are the two types of signaling molecules?
A
hydrophobic / hydrophilic
2
Q
What are the two general classes of receptors
A
cell surface and intracellular
3
Q
What is a gap junction and what type of signaling molecules can pass through it
A
small pore between cells, small signaling molecules only
4
Q
What is required for a cell to respond to a signal
A
correct receptor and “signaling machinery” inside the cell
5
Q
Acetylcholine
A
contraction in skeletal muscle cells
relaxation in heart muscle cells
signaling in secretory cells
3 responses from the same signal
6
Q
Paracrine signaling
A
local signal
7
Q
Synaptic signaling
A
long range - neurotransmitter signal from axons
8
Q
Endocrine signaling
A
long range - hormones / blood stream
9
Q
Autocrine signaling
A
short lived / self signaling
10
Q
What are the classes of hydrophobic signaling molecules
A
steroids hormones
thyroid hormones
retinoids
11
Q
Steroids
A
planar structure made from cholesterol
12
Q
Examples of steroid hormones
A
cortisol (made by adrenal gland on top of kidney)
estradiol (ovary)
testosterone (testis)
vitamin D (made in skin)
13
Q
Thyroids hormones
A
made from tyrosine
14
Q
Hsp
A
heat shock protein
15
Q
What are the domains of intracellular receptors
A
activation domain
ligand binding domain
DNA binding domain
16
Q
When intracellular receptors are in the cytosol
A
They are bound to an inhibitory complex (chaperone)
17
Q
What happens when a signaling molecule binds an intracellular receptor
A
molecule binds and displaces HSP
causes a conformational change and exposes DNA binding domain
Goes to nucleus and acts as a transcription factor
18
Q
What is the first response of intracellular receptors
A
Early Primary Response
19
Q
What happens in the early primary response?
A
signal binds to receptor
receptor goes to nucleus and acts as transcription factor
Increases transcription / translation of proteins in ~30 minutes
**Makes early response proteins
20
Q
What is the second response of intracellular receptors
A
Secondary Response
21
Q
What happens in the secondary response of intracellular receptors?
A
Early response proteins act in a neg. feedback loop turn off transcription of primary response genes.
Early response proteins increase transcription/translation of secondary response proteins.
**Cells can change behaviors
22
Q
Hydrophilic signaling molecules aka
A
soluble signaling molecules
23
Q
What are the two types of proteins in relay systems within cells
A
proteins that become phosphorylated
proteins that bind GTP (called G proteins)
24
Q
Both phosphorylation / dephos and GTP - GDP act to
A
turn signal molecules on and off
Phos = on GTP = on
25
G Protein receptors can
activate adenyly cyclase
inhibit adenyly cyclase
activate phospholipase C (PLC)
26
Steps in G protein signaling
Receptor becomes activated when it binds the ligand
This receptor then interacts with the G protein
Binding activates the G protein
G protein then activates the next protein
27
G protein linked cell surface receptor structure
```
7 pass proteins
N terminus binds ligand
C3 look (3rd cytoplasmic) specifies which G protein interacts
```
28
What do GAPs and RGSs do to G proteins?
increase rate of GTP hydrolysis and turn G proteins off
29
Many G proteins regulate ________levels
cAMP
30
cAMP is a
secondary messengers
31
what are the 2 types of heterodimeric G proteins
stimulatory G proteins (Gs)
| Inhibitory G proteins (Gi)
32
Which enzyme controls cAMP levels
adenylyl cyclase
33
cAMP cycles to what that is NOT a signaling molecule
5'AMP
34
What is contained on the alpha subunit of a Gs protein
nucleotide binding domain and GDP binding pocket
35
How does adenylyl cyclase make cAMP
from ATP
36
How do Gs proteins work
ligand binds and causes conformational change
G protein binds receptor and alpha subunit binds GTP
alpha subunit diffuses away from beta and gamma subunits.
alpha subunit moves through membrane and interacts with second enzyme
ATP becomes cAMP
alpha subunit hydrolyzes GTP back to GDP and associates with beta and gamma subunits
cycle will repeat
37
How does cholera work like a Gs protein
modifies subunit so that it can't hydrolyze GTP
38
How does pertussis work like a Gi protein
locks the alpha subunit in the GDP phase
39
True or False: Many different G coupled protein receptors are able to turn on Gs proteins
True....means many different ligands can turn on the same receptors.
40
How do Gi proteins work
ligand binds receptor
receptor interacts with Gi protein
alpha subunit will interact with adenylyl cyclase but will inhibit it
41
How do they know it is the C3 loop of the G protein coupled receptor that makes it specific
Use recombinant DNA tech to swap out this sequence and you get a different receptor.
42
GPCR
G protein coupled receptor
43
What rises in the intracellular space when Gs activates adenylyl cyclase?
levels of cAMP
44
Kinases
phosphorylate proteins
45
PKA
protein kinase A
46
When is PKA inactive
When all 4 subunits are bound together
47
How is PKA activated
cAMP binds regulatory subunit and causes conformational change
This releases the catalytic domain
PKA then phosphorylates other proteins
48
What are some examples of cellular changes caused by PKA
glycogen breakdown
alterations in transcription
release of fluid across epithelial cells (membranes)
49
How are receptors involved in signal amplification
Each receptor can stimulate many different G proteins
50
How does cAMP activation cause glycogen breakdown in muscle cells?
Ligand binds receptor which activates cAMP.
cAMP turns on PKA
PKA phosphorylates phosphorylase kinase (activates it)
This enzyme activates glycogen phosphorylase
This enzyme turns glycogen to glucose 1 phosphate that feeds into respiration cycles.
51
WHY is cAMP generated in times of stress?
| What signaling molecule is the ligand?
cAMP causes glycogen to break into glucose which then becomes ATP
Adrenaline is the ligand
52
How does PKA (due to cAMP) change gene expression
PKA enters nucleus and phosphorylates CREB
| CREB (activated) binds P300/CBP to create transcription factors (loosens DNA around histones)
53
What does CREB stand for
cAMP response element binding protein
54
How does PKA (due to cAMP) release fluid in epi cells
after increase in cAMP and then in PKA...
| This signaling creates a gradient that will draw water by osmosis
55
Movement of water across epithelial cells relies on what protein
CFTR = cystic fibrosis transmembrane conductance regulator
CFTR = membrane of ABC superfamily of proteins
Uses ATP but NOT a pump because moves things down the concentration gradient
56
What are the main domains of the CFTR protein
```
MSD = membrane spanning domain
NBD = nucleotide binding domain
R = regulatory domain *turns CFTR on / off
```
57
How is CFTR activated by cell signaling
PKA turns CFTR on (activates it)
58
CFTR normally
Moves Cl- ions from cells into mucus causing water to follow and thin mucus
59
How do mutations stop CFTR from working
Most common will delete Phe at 508
Causes misfolded protein
Induces unfolded protein response so receptor is degraded in cytosol
Most of the people with the mutation are missing the receptor all together.
60
If you are heterozygous for a mutation in the CFTR gene it gives you an advantage to survive
Cholera. Cholera locks the CFTR in the on position. Lower levels of CFTR means less water loss
61
How does cholera affect CFTR
Cholera turns off CFTR because it locks the Gs into the "on" position. So, constantly moving ions and you lose large amounts of water into intestines
62
How does pertussis affect CFTR
locks Gi in off position. So, CFTR continues to move ions and therefore water out of cells. Lungs fill with fluid.
63
PLC
Phospholipase C
64
IP3 and Ca +2 ions
| cAMP
are secondary messengers
65
What is the basic pathway of signal transduction through membrane receptors
Ligand binds receptor (in membrane)
Receptor interacts with G protein
G protein activates and enzyme
The enzyme activates secondary messengers
Secondary messengers act on target molecules
66
PIP2 is cleaved to create
DAG and IP3 secondary messengers
67
What are some ways that Ca+2 levels are kept very low in cells
Ca-ATPase
Ca binding proteins
Pumps
Na+/Ca+2 antiporter
68
Why is Ca+2 concentration kept low in cells
It is a very powerful signaling molecule
69
Gq linked receptors generate
IP3
70
How does the Gq protein work
*like Gs
Activated alpha subunit interacts with PLC and activates it
Activated PLC cleaves into DAG and IP3
IP3 goes to the ER and releases Ca+2 ions into cytosol
PKC uses the Ca+2 ions and then goes on to change gene expression (usually)
71
Orail
plasma membrane associated Ca+2 channel
72
Stim =
stromal interaction molecule
| An ER membrane protein that binds Ca+2 ions
73
What happens in ER after IP3 signal
ER moves Ca ions to cytosol
Decrease in Ca in ER triggers STIM dimers and conformational change
The STIM dimers interact with Orail
74
What is the G Protein-Ca/IP3 pathway that leads to activation of transcription factors and modulation of gene expression
DAG binds to PKC and activates it
PKC phosphorylates MAP kinase and activates it
MAP kinase moves to nucleus and phosphorylates transcription factors
PKC also phosphorylates IK-B and it releases NF-KB
NF-KB moves to nucleus and works as transcription factors
75
Enzyme linked receptors
Have catalytic activity and are active when bound to a ligand
76
Receptor tyrosine kinases are
an example of enzyme linked receptors
77
What are some examples of receptor tyrosine kinases receptors
```
NGF (nerve growth factor)
PDGF (platelet derived growth factor)
FGF (fibroblast derived growth factor)
EGF (epidermal derived growth factor)
VEGF (vascular endothelial growth factor)
```
78
What do receptor tyrosine kinases do
phosphorylate tyrosines
79
How are receptor tyrosine kinases activated
When no ligand bound they are monomers and when a ligand binds they dimerize. This dimerization will activate them.
80
What are the three domains of a RTK
extracellular ligand binding domain
transmembrane alpha helix
cytosolic domain with the tyrosine kinase activity
81
After RTKs are dimerized what is the first step
Autophosphorylation of multiple tyrosines on the receptor itself.
82
Ras is active / inactive when
```
active = bound to GTP
inactive = bound to GDP
```
Ras is a monomeric G protein
83
GAP =
GTPase activating protein
84
Why does RAS need GAP to work
its own GTPase activity is very low.
85
The cell cycle is regulated by proteins within the cell at what points
in G1 just before S
in G2 just before M
in M just before metaphase
86
heterokaryon
has double the amount of DNA
87
MPF
mitosis promoting factor (a dimer)
88
CDK
cyclin dependent kinase
| phosphorylates other proteins
89
WHat causes CDK to become active
binding to specific cyclins
| different cyclins are made / degraded with every phase of every cell cycle
90
What are the main classes of cell cycle control system
G1-S phase CDKs
S phase CDKs
Mitotic CDKs
APC/C activity
91
Proteosomes
large protein complexes that degrade proteins that have been ubiquinated
92
Rb
retinoblastoma
an inhibitor of E2F transcription factor
Turned off by phosphorylation and releases E2F. This causes transcription of G1 cyclins
93
What can cause retinoblastoma tumors in the eye
No function of Rb so E2F is always active and G1 always moves into S because it induces S phase cyclins.
94
Role of Sic 1
keeps S phase cyclin-cdk "off" in G1
| When sic 1 is phosphorylated and tagged for degradation then DNA replication is initiated by S phase Cyclin-CDK
95
Role of active S phase cyclins
phosphorylate proteins in ori rep. complex and cause conformational change.
Proteins fall off and ori remains active
96
What is the role of Mad2 in the spindle assembly checkpoint
Mad2 inhibits proteosome that degrades securin if the spindle is not properly formed
97
Chromosome segregation checkpoint
If chrs. not at poles, then inhibit cdc14
| Cdc14 promotes degradation of mitotic cdks
98
ALL DNA damage checkpoints:
| in G1, before S phase entry, During S phase, in G2
Use p53
99
IF DNA has not replciated
ATM/R activates p53 which activates P2ICIP which inhibits cyclin/cdk dimers and pauses cell cycle
ATR activates CHK 1 which inhibits Cdc25C. (This is the protein that moves cell to M phase)
100
p53
is a transcription factor
| unstable unless there is DNA damage
101
Unipotent
can only form one differentiated cell type
102
Multipotent
can form multiple types of differentiated cells
103
Pluripotent
can form all of the different cell types
104
Totipotent
can form all of the differentiated cell types + specialized tissues
