Cell Communication Flashcards
(100 cards)
1
Q
define signal transduction
A
cell to cell communication
2
Q
in general how does signal transduction work?
A
- extracell signal binds to receptor protein on memb.
- binding causes an intracell signal to be released
- intracell signal activates effector proteins
- effector proteins cause the outcome
3
Q
what are 3 outcomes of effector proteins?
A
- altered metabolism
- altered gene expression
- altered cell shape or mvt
4
Q
more specific signal transduction definition
A
extracellular signaling molecules bind to specific receptors in target cells to initiate a chain of events
5
Q
external signals induce 2 major types of responses
A
- fast response
2. slow response
6
Q
fast response
A
change in activity or function of enzymes or proteins in cell
7
Q
slow response
A
change in amounts of proteins by change in gene expression
8
Q
signal transduction process
A
- ligand
- high affinity receptors
- intracell signal proteins
- effector proteins
- outcome
9
Q
list the types of signaling
A
- endocrine
- paracrine
- synaptic
- autocrine
- direct cell
10
Q
long distance signaling
A
endocrine signaling
11
Q
endocrine signaling
A
long distance, long half-life
signal enters blood stream and travels to reach it’s target
12
Q
local signaling
A
paracrine signaling
or
synaptic signaling
13
Q
paracrine signaling
A
local, not freely diffusible
affects the nearby cells
14
Q
synaptic signaling
A
acts locally
affects nearby axons/dendrites using neurotransmitters
15
Q
signals to the cells that released the signal
A
autocrine signaling
16
Q
autocrine signaling
A
cell releases a signal to affect itself and/or cells of same type nearby
ex. growth factors
17
Q
immune cell signaling
A
direct cell signaling
ex. Ag presenting to T cells
18
Q
each cell interprets all the signals it gets to determine what to do…..
A
survive
die
divide
differentiate
19
Q
signals
A
or ligands
typically secreted via exocytosis
signal types decides where signal goes
20
Q
receptors
A
bind specifically to signal molecules w/ high affinity
because signals are produced in low levels
21
Q
effectors
A
the targets of receptors intracell
alter cell activity to create 2nd messengers
22
Q
main types of ligands
A
- small lipophilic - hormones
2. water soluble molecules or hydrophilic
23
Q
general types of receptors
A
- cell surface receptors
2. intracellular receptors
24
Q
describe intracellular receptors
A
steroid receptors - can be present in cytosol since the signal can easily pass thru the bilayer
25
7 transmembrane receptors
or G-protein coupled receptors
26
describe the structure of G-protein coupled receptors
have 3 domains
1. extracell - binds ligands
2. transmemb. - anchors
3. cytoplasmic domain - associates w/ G protein
27
G-proteins
heterotrimeric proteins composed of 3 subunits (a b g)
GTP or GDP
28
describe the steps of G-protein relaying signals
1. ligand binds receptor
2. conformational change occurs in receptor
3. receptor binds to G
4. receptor acts as GEF
5. GDP exchanged for GTP
6. Ga is now active an binds to effector to activate it
29
adenylyl cyclase
an effector protein that catalyzes formation of cAMP
which is the 2nd messenger that can cause a biological response
30
reset of G-protein system
hydrolysis of GTP bound to Ga occurs
Ga inactivated and recycled/sent back to starting point
31
what is the significance of a G-protein coupled receptor acting as a GEF?
guanine exchange factor
it exchanges the GDP for a GTP which causes Ga to become activated
***it exchanges, not phosphorylating***
32
Gas
stimulating Ga type
stims adenylyl cyclase
33
Gai
inhibiting Ga type
inhibits adenylyl cyclase
34
cAMP
a 2nd messenger
activates a protein kinase called PKA
35
PKA
a protein kinase activated by cAMP
can phosphorylate proteins to either activate or inactivate them
36
PKA structure
inactive form - has 4 subunits
2 catalytic, 2 regulatory
active form - the 2 catalytic units released as separate entities
37
binding of cAMP to PKA
2 cAMP binds to each regulatory subunit (so 4 total)
causes the 2 catalytic units to be released from the regulatory units
38
how does phosphorylation change a proteins function?
it changes the shape of the protein
| and protein shape determines it's function
39
what is meant by amplification of signaling?
a single ligand receptor event can activate multiple effector protein to generate hundreds of 2nd messengers which effect 1000's of proteins
40
what is desensitization of a signal?
ability to turn off or reject the signal
important for preventing cancer cell growth
41
list the 5 ways to stop a signal in a signal transduction pathway
1. receptor sequestration
2. receptor destruction
3. hormone level drop
4. signal removal
5. GRKs
42
receptor sequestration
invagination of the membrane to take the receptor off the cell surface
thus the cell cannot receive signals
43
receptor destruction
cell invaginates the signal
the endosome combines w/ lysosomes
receptor protein destroyed
thus the cell cannot receive signals
44
dropage of hormone levels
decreases adenylyl cyclase activity
which decreases cAMP
which decreases PKA
thus decreases/stopping the signal transduction pathway
45
removal of signaling molecules
phosphodiesterase will remove cAMP
thus no 2nd messenger - no outcome
46
define GRKs
G-protein receptor kinases
capable of phosphorylating G-protein coupled receptors
47
GRK effects
1. phosphorylates a receptor
2. now the protein arrestin will bind
3. results: receptor cannot act as GEF
thus signal pathway stopped since Ga cannot be activated
48
arrestin
- -a protein that can bind to a G receptor after GRK binds
- -binds to the 3rd intracell loop
- -which prevents Ga from interacting w/ loop 3
resulting in Ga not being converted to Ga-GTP
49
PKA: addition of 2 negative charges can change ….. ?
the conformation of the protein thus changing it's function
50
GPCR
G-protein coupled receptor
51
other G-protein variants
Gao
| Gaq
52
variant G-protein GPCR pathway: signal to 2nd messengers
1. ligand binds
2. GPCR binds Gao/q
3. GPCR acts as GEF
4. active Ga binds to phospholipase C
5. phospholipase C cleaves PIP2
6. produces IP3 and DAG
53
IP3
produced when phospholipase C cleaves PIP2
binds to IP3 ligand gated channels on ER to trigger opening to release Ca into cytosol
54
DAG
produced when phospholipase C cleaves PIP2
works w/ Ca to activate PKC
55
PKC
protein kinase C
Ca and DAG both bind to and activate PKC
PKC undergoes conformational change and can now phosphorylate a variety of substrates
56
2 roles of Ca discussed in cell signaling
1. working w/ DAG to activate PKC
| 2. binding to calmodulin to activate it
57
calmodulin
Ca binds to activate it
can bind to different cellular proteins to activate their functions
58
calmodulin example
binds to CaM kinase II
which can then phosphorylate transcription factors to induce transcription
59
list the other 3 types of signal transduction
1. tyrosine kinases
2. jak-stat receptors
3. serine/threonine kinases
60
RTK purpose
play important role in signal transduction
are used in response to growth factors
growth factor = ligand/signal
61
RTK domains
1. extracellular domain
2. transmembrane domain
3. cytoplasmic/enzymatic domain
62
RTK extracellular domain
ligand binding
| ligand for R7 = Boss
63
RTK ligand binding
- -causes conformational change
- --2 receptors dimerize
- ---autophosphorylation occurs
64
autophosphorylation
occurs in ligand bound RTK receptors
causes receptors to act as scaffolding/docking sites to recruit other proteins to plasmalemma
65
RTK transmembrane domain
anchors the receptor in the plasmalemma
66
RTK cytoplasmic domain
- -has a tyrosine kinase domain that acts as enzymatic domain
- -where the signal transmits thru
67
what does RTK signal transmittance thru ______ result in
thru tyrosine kinase domain to phosphorylate protein attached
68
RTK pathway
1. growth factor binds
2. RTK dimerize, autophosphorylate
3. RTK binds to SH2 of Grb2
4. SH3 of Grb2 binds to SOS via prolines
5. SOS acts as GEF to Ras
6. Ras-GTP binds to Raf
7. active Raf initiates Map kinase pathway
69
what does the Map kinase pathway lead to?
changes in gene expression
to result in cell proliferation
70
what are the more direct routes for impacting transcription?
1. jak-stat
| 2. smad
71
what initiates the MAP kinase cascade
activate Raf via the binding of Ras
72
MAP kinase cascade is propagates the signal downstream by using ?
ATP to phosphorylate the next substrate
73
list the Map kinase cascade
1. Raf activates Mek
2. Mek activates Erk
3. Erk enters nucleus
resulting in changes in gene transcription to cause cell proliferation
74
map kinase kinase kinase
raf
75
map kinase kinase
mek
76
map kinase
erk
77
MAP
mitogen activated protein kinase
results in cell proliferation
78
JAK-STAT pathway
1. ligand binds receptor
2. receptors dimerize
3. 2 jaks bind
4. jaks phosphorylate each other and receptors
5. receptor binds 2 stats and phosphorylate them
6. stats separate, dimerize, enter nucleus, bind to DNA
7. causing transcription of target genes
79
janus kinases
JAK
80
many signaling molecules are ________ that can mutate into oncogenes and cause _____ .
protooncogenes and cause cancer
81
STAT
signal transducer and activators of transcription factors
82
example of jak-stat pathway
kidneys produce erythropoietin which employs the jak-stat to initiate signaling to result in increased production of RBCs
83
R-Smad =
receptor specific smad
84
Co-Smad =
common smad
85
R-smad forms a complex w/ ?
co-smad
86
how is the receptor activated in the smad pathway?
via phosphorylation
87
Serine/Threonine pathway
= smad path
1. receptor activated
2. receptor binds to r-smad and phosphorylates it
3. active r-smad dissociates and binds to co-smad to create complex
4. complex moves into nucleus
5. impacts target genes for transcription
88
what the example of the smad pathway used in class?
hereditary hemochromatosis
iron metabolism - expression of hepcidin
89
hepcidin
protein made in liver that regulates the uptake of Fe
binds to Ferroportin in intestinal cells to cause invagination and proteolysis of ferroportin
90
high hepcidin levels
= no fe uptake
91
low hepcidin levels
= fe uptake via Ferroportin in intestines
92
iron pathway: food to blood stream
enters intestinal cells via DMT1 on apical surface
exits cell into blood via Ferroportin on basal domain
93
hereditary hemochromatosis
--genetic disease of uncontrollable iron absorption, leading to fe overload and organ failure
---due to mutations in hfe gene -- also called C282Y mutation
94
significance of hfe gene
hfe binds to transferrin receptors
if mutated it cannot turn on hepcidin expression
thus no control of ferroportin
95
hfe works thru a ___ pathway
smad
96
a mutated hfe cannot signal _____ to do ?
tfR2
| to start smad path to express hepcidin
97
point mutation in codon 12
results in Gly replaced w/ Val
this constitutively activates Ras
which is always found in human cancer
98
how is protein kinase C activated?
1. signal binds GPCR
2. GPCR acts as GEF to Gao/q
3. activates phospholipase C
4. it cleaves ip2
5. producing ip3 and dag
6. ip3 causes er to release Ca
7. dag + Ca bind to PKC to activate it
99
describe how a mutation in hfe causes a signal transduction problem? and what does it lead to ?
if hfe is mutated it cannot bind to tfr2 to activate the smad pathway that leads to expression of hepcidin. if hepcidin is not present to regulate Ferroportin activity, this leads to iron overloading-uncontrollable absorption of iron.
leading hereditary hemochromatosis
100
hfe binds to ?
TfR2
