5 - Cell Signaling (Part 1) Flashcards
1
Q
-Mechanism for responding to physical and chemical changes in theri environment
A
Cell signaling
2
Q
Principles of cell signaling: Mechanisms for responding to _______ and _______ changes in their environment
A
Physical and chemical
3
Q
Principles of cell signaling: _________ sensing in bacteria
A
Quorum
4
Q
Allow bacteria to coordinate their behavior
A
Quorum sensing
5
Q
Principles of cell signaling: Mating factor in ________
A
yeasts
6
Q
Communication between cells in multicellular organisms is mediated mainly by
A
extracellular signal molecules
7
Q
_______ activates the receptor which in turn activates one or more intracellular pathways or systems
A
Binding
8
Q
The extracellular signal molecule is recieved by the ___________________
A
Receptor protein
9
Q
The effector proteins recieves the _____________
A
intracellular signaling proteins
10
Q
Processes the signal inside the recieving cell and distribute it to the appropriate intracellular targets
A
Intracellular signaling proteins
11
Q
The target that lie at the end of signaling pathways
A
Effector proteins
12
Q
What are the 3 effector proteins?
A
- Metabolic enzyme
- Transcription regulatory protein
-Cytoskeletal protein
13
Q
As the metabolic enzyme recieves the intracellular signaling proteins, it leads to _____
A
altered metabolism
14
Q
As the transcription regulatory protein recieves the intracellular signaling proteins, it leads to _____
A
altered gene expression
15
Q
As the cytoskeletal protein recieves the intracellular signaling proteins, it leads to _____
A
altered cell shape or movement
16
Q
What are 4 main molecule and proteins involved in cell signaling?
A
-Extracellular signal molecule
-Receptor protein
-Intracellular signaling proteins
-Effector proteins
17
Q
Explain the function of these molecule and proteins
A
The extracellular signal molecul is recieved by the receptor protein in order to pass through the plasma membrane. This signal molecule is then carried by the intracellular proteing along the cytosol to the efffector protein whch is responsible for regulating biological activities.
18
Q
What are the 4 types of intracellular cell signaling
A
- Contact- Dependent signaling
-Paracrine Signaling - Synaptic Signaling
- Endocrine Signaling
19
Q
a type of paracrine signaling where cells produce signals that they themeselves respond to
A
Autocrine signaling
20
Q
Cell signaling that utilizes neurons; chemical synapses
A
Synaptic signaling
21
Q
Cell signaling that realeses hormones into the bloodstream to be recieved by the target cell
A
Endocrine signaling
22
Q
Often receptors on the target cell surface
A
Transmembrane proteins
23
Q
A cell signaling where the membrane- bound signal molecule from the signaling cell is directly recieved by the receptor of the target cell
A
Contact- dependent signaling
24
Q
A cell signaling where secreted molecules diffuse locally and trigger a response in neighboring cells
A
Paracrine signaling
25
2 types of receptors taht communicate by extracellular signal molecules
- Cell- Surface Receptors
- Intracellular Receptors
26
Signal molecules bind to cell-surface receptors, which in turn generate signals inside the target cell
Cell- surface receptors
27
Examples/kinds of extracellular signal molecules
Proteins, small peptides, nucleotides, steroids, retinoids, fatty acid derivatives, and even dissolved gasses such as nitric oxide and carbon monoxide
28
Signal molecules can diffuse across the plasma membrane and bind to recepto proteins inside the target cell
Intracellular receptors
29
- Has high specificity of binding site of receptors
Target cell
30
An extracellular signal molecule
ligand
31
4 stages of cell
- Cell survival
- Cell proliferation
- Terminal differentiation
- Cell apoptosis
32
Each cell is programmed to respond to specific combinations of _____________ _______
Extracellular signals
33
These extracellular signals are either _________ or __________
Stimulatory or inhibitory
34
Cell responds tot he signals ____________
Selectively
35
To determine how a cell integrates all of this signaling information in order to make decisions- _____, _______, ________, and so on
to divide, to move, to differentiate
36
Programed cell death
cell apoptosis
37
Differentiation into a non dividing state
Terminal differentiation
38
a signal molecule often has different effects on different type of _______ _______
target cells
39
Example of signal molecule that has different effects on different type of target cells
Acetylcholine
40
Acetylcholine causes differences in the ______________, _________________, and ________________
intracellular signaling proteins, effector proteins, and genes
41
An extracellular signal simply induces the cell to respond according to its ___________ ________
Predetermined state
42
Acetylcholine in heart pacemaker cell causes
decreased rate of firing
43
Acetylcholine in salivary gland cell causes
Secretion
44
Acetylcholine in skeletal muscle cell causes
contraction
45
Three major classes of cellsurface receptor proteins
- Ion-Channel Coupled transporters
- G-Protein Coupled Receptors
- Enzyme- Coupled Receptors
46
These classes of cell-surface receptor proteins act as
Signal transducers
47
Converting an extracellular ligand-binding event into intracellular signals that alter the behavior of the target cell
Signal transducers
48
The ion- channel coupled receptors is also known as
transmitter- gated ion channels or ionotrophic receptors
49
Contains electrically excitable cells and neurotransmitters
ion- channel coupled receptors
50
Involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells
Ion- channel coupled receptors
51
Ion- channel coupled receptors are mediated by ____________
neurotransmitters
52
contains Plasma- membrane- bound target protein (enzyme or ion channel), and trimeric GTP- binding protein (G protein)
G- protein- coupled receptors
53
Acts by indirectly regulating the activity of a separate plasma- membrane - bound target protein, which is generally either an enzyme or an ion channel
G- protein- coupled receptors
54
Mediates the interaction between the activated receptor and this target protein
Trimeric GTP- binding protein (G protein)
55
3 components of G- protein- coupled receptors
- inactive receptor
- inactive G protein
- Inactive enzyme
56
Function as enzymes or associated directly with enzymes
Enzyme- coupled receptors
57
Single- pass transmembrane proteins that have their ligand- binding site outside the cell and their catalytic or enzyme binding site inside
Enzyme- coupled receptors
58
Enzyme- coupled receptors: Ligand binding is __________ the cell
outside
58
59
Enzyme- coupled receptors: Enzyme- binding site is ________ the cell
inside
60
Phosphorylate specific sets of proteins in the target cell when activated
Protein kinases
61
First messengers
Extracellular signals
62
Second messengers
Intracellular signaling molecules
63
Intracellular signaling molecules carries
- small chemicals
- water- soluble molecules
- lipid- soluble
64
example of water- soluble molecule
Cyclic AMP (cAMP) & Ca+
65
example of a lipid- soluble molecule
diacylglycerol
66
Pass the signal by ________ to and _______ the behavior of selected signaling or effector proteins
Binding and altering
67
Intracellular signaling molecules often behave as
molecular switches
68
2 types of intracellular
signaling proteins that act as
molecular switches
- signaling by phosphorylation
-signaling by GTP binding
69
The largest class of molecular switches consists of proteins that are activated or inactivated by
Phosphorylation
70
Addition of Phosphate group
Kinase
71
Example of kinases
- serine- threonine kinase
-tyrosine kinases
72
removes the phosphate group
Phosphatase
73
Human genome encodes ___ kinases; ___ phosphatase
520 kinases; 150 phosphatase
74
Other important class of molecular switch
GTP- binding protein
75
Bound GTP
on
76
Bound GDP
off
77
Types of GTP- binding proteins
- trimeric GTP- binding proteins (G proteins)
- monomeric GTP- binding proteins (small monomeric GTPases)
78
Help relay signals from G- protein- coupled receptors that activate them
trimeric GTP- binding proteins (G proteins)
79
Help relay signals from many classes of cell-surface receptors
monomeric GTP- binding proteins (small monomeric GTPases)
80
Drive the proteins into an "off state; increasing the rate of hydrolysis of GTP
GTPase- activating proteins (GAPS)
81
Drive the proteins into an "on" state; release bound GDP
Guanine Nucleotide exchange Factors (GEFs)
82
Contains a series of activation steps
Signaling pathway
83
A sequence of two inhibitory steps can have the same effect as one activating step
Double negative activation
84
An activated intracellular sigaling molecule should interact only with the appropriate _____ targets, and likewise, the targets should only be activated by the appropriate ________ signal
downstream; upstream
85
Ways that a signal remain precise
- high affinity and specificity
- high affinity and specificity
86
complementary surfaces
high affinity and specificity
87
Respond only when the upstream signal reaches high concentration or activity level
high affinity and specificity
88
Involves scaffold proteins
localization
89
form signaling complexes
scaffold proteins
90
Functions of scaffold protein
- holds the protein in close proximity
- interact at high local concentration
- sequentially activated rapidly
91
form only transiently in response; around a receptor
scaffold proteins
92
Phosphorylated cytoplasmic tail of receptor serve as __________ ________
docking sites
93
Receptor activation leads to production of _____________
Phosphoinositides
94
recruit specific intracellular signaling proteins
Phosphoinositides
95
Three types of intracellular
signaling complexes.
- Preformed signaling complex on a scaffoled protein
- Assembly of signaling complex on phosphoinositide docking sites
- Assembly of signaling complex on an activated receptor
96
To detect and measure a specific stimulus in one location of a cell and then generate an appropriately timed and measured response at another location
1. response timing
2. sensitivity to extracellular signals
3. dynamic range
4. persistence
5. signal processing
6. integration
7. coordination
97
number of affinity; amplification
sensitivity to extracellular signals
98
responsiveness
dynamic range
99
transient response; prolonged or permanent
persistence
100
switchlike response; oscillatory response
signal processing
101
multiple inputs
integration
102
multiple responses
coordination
103
speed of response depend on the nature of
intracellular signaling molecules
104
changes in proteins
rapid responsec
105
hanges in gene expression and the synthesis of new proteins
usually requires many minutes or hours
106
response fades when
signal ceases
107
-smoothly graded response
- concentration rises beyong some treshold value
hyperbolic response
108
generates significant responses only when the signal concentration rises beyond some treshold value
abrupt responses
109
2 types of abrupt response:
- sigmoidal response
- discontinous or all- or- none
110
low concentrations of stimulus do not have much effect, but then the response rises steeply and continously at intermediate stimulus levels
Sigmoidal response
111
the output of a process acts back to regulate that same process
feedback loops
112
output inhibits its own production
negative feedback
112
output stimulates its own production
positive feedback
113
steepen the response- sigmoidal or all-or-none response
Positive feedback
114
- can exist in either a "switched off" or a "switched- on state"
- a transient exracellular signal can induce long-term changes
bistable
115
-muscle cell specification
- all-or-none response
-all cells in a population do not respond identically to the same concentration of extracellular signal
positive feedback
116
counteracts the effect of a stimulus
negative feedback
117
Negative feedback limits the level of the
response
118
a delayed negative feedback with a long enough delay can produce responses that
oscillate
119
stimulus suddenly increased
adaptations
120
-prolonged exposure to a stimulus decreases the the cell's response to that level of stimulus
- respond to changes in the concentration of an extracellular signal molecule
adaptation or desensitization
121
122
123
124
a strong response modifies the signaling machinery that reset itself to become
less responsive
124
Some ways in which target cells can become adapted (desensitized) to an extracellular signal molecule
- Receptor Sequestration
- Receptor Down- Regulation
- Receptor Inactivation
- Inactivation of Signaling Protein
- Production of Inhibitory Protein
124
Such signal- induced receptor endocytosis leads to the destruction of the receptor in lysosome
Receptor- down regulation
125
Largest family of cell-surface receptors
G-protein- coupled receptors
126
_____, _____, and______ depend on the G-protein- coupled receptors
sight, smell, and taste
127
G-protein- coupled receptors consists of a sing polypeptide chain that threads back and forth across the lipid bilayer _____ times, forming a _________
seven; cylindrical structure
128
relay the signal into the cell interior
G-proteins
129
relay signal sform GPCRs, couples the receptor to enzymes or ion channels in the membrane
trimeric GTP- Binding proteins (G-protein)t
130
3 subunits of the G proteins
a, B, and y
131
a subunit has GDP bound and the G protein is inactive
unstimulated
132
acts like guanine nucleotide exchange factor (GEF)
activation
133
what occurs when the a subunit release its bound GDP?
-a subunit release its bound GDP
-binding of GTP
-conformational changes
-dissociation of the GTP bound Ga subunit from the GBy pair
134
synthesized from ATP by adenylyl cyclase
cyclic AMP (cAMP)
135
responsible for the synthesis of cAMP
adenylyl cyclase
136
responsible for the destruction of cAMP
phosphodiesterases
137
regulate the production of cAMP
G proteins
138
activates adenylyl cyclase
Gs (stimulatory G protein)
139
inhibits adynylyl cyclase
Gi (inhibitory G protein)
140
causes ADP ribosylation that alters the Gs a subunit; leading to inactivation
cholera toxin (cholera, severe diarrhea)
141
causes ADP ribosylation of the a subunit of Gi
pertussis toxin (pertussis or whooping cough)
142
In most animal cells, cAMP exerts its effect by mainly activating
cyclic- AMP dependent protein kinase (PKA)
143
Phosphorylates specific serines and threonines, regulating their activity
kinase
144
two catalytic subunits and two regulatory subunits
inactive stae
145
released catalytic subunit
activated state
146
Otejr responses mediated by cAMP depends changes in the transcription of
specific genes
147
cAMP activates the gene that encodes this hormone
Somatostatinor
148
a short cis-regulatory protein contained by the somatostatin gene
cyclic AMP response element (CRE)
149
Transcription regulator
CRE- binding (CREB) protein
150
CBP
CREB- Binding Protein
151
Many GPCRs exert their effects through _____ that activate the plasma- membrane- bound enzyme ____________
G proteins; phospholipase C-B (PLCB)
152
phospholipase C-B (PLCB) acts on
inositol phospholipid signaling pathway
153
activates phospholipase C-B
Gq
154
The activated phospholipase then cleaves the PI(4,5)P2 to generate two products
diacylglycerol & inositol 1, 4, 5-triphosphate (IP3)
155
A water- soluble second messenger
IP3
156
IP3- gated Ca2+- release chanels
IP3 receptors
157
IP3 increases concentration of ____ in the ______
Ca2+ ; cytosol
158
activate protein kinase C (PKC)
diacylglycerol
159
G protein called ___ activates GEF (guanine nucleotide exchange factor) that activates a monomeric GTPase (Rho family) which regulates the ______ _______
G12; actin cytoskeleton
160
In some cases, G proteins directly activate or inactivate _______ in the plasma
ion channels
161
smell and vision depend on _____ that regulate ion channels
GPCRs
162
- act through cAMP
Olfactory receptors
163
activates adenylyl cyclase
olfactory specific binding G protein (Golf)h
164
how many olfactory receptors in human
350
165
Each ______ activates its own characteristic set of olfactory receptor neurons
odorant
166
Also involved in vision
cyclic nucleotide- gated ion channels- cyclic GMP
167
responsible for synthesizing cyclic nucleotide- gated ion channels
guanylyl cyclase
168
responsible for degradation of cyclic nucleotide- gated ion channels
cyclic GMP phosphodiesterase
169
fastest G-protein- mediated response in vertebrates
Vision transduction responses
170
receptor activation stimulated by light causes a fall in the level of
cyclic nucleotide
171
non color vision in dim light
rod photoreceptors (rod)
172
color vision in bright light
cone photoreceptors (cones)
173
-stack of discs; contans cyclic GMP- gated cation channels
phototransduction apparatus
174
cyclic GMP bound
dark
175
_____ causes hyperpolarization
light
176
decreases the cyclic GMP concentration and closes the cation channel
hyperpolarization
177
activated by a photon of light
Rhodopsin
178
rhodopsin alters conformation of
G protein transducin (Gt)
179
effect of rhodopsin
- alters conformation of G protein transducin (Gt)
- activate the cyclic GMP phosphodiesterase
- hydrolyzes cyclic GMP
- GMP levels fall
180
rods use _________________ to allow the cells to revert quickly to a resting, dark state in the aftermath of a flash light
negative feedback loops
181
it phosphorylates rhodopsin, inhibiting the ability of the rhodopsin to activate transducin
rhodopsin kinase (RK)
182
an inhibitory protein, binds to the phosphorylated rhodopsin, further inhibiting its activity
arrestin
183
(I)activates adenylyl cyclase; activates Ca2+ channels
a Gs
184
(I)Activates adenylyl cyclase in olfactory sensory neurons
a Golf
185
(II)Inhibits adenylyl cyclase
a Gi
186
(II)Activates K+ channels
By Gi
187
(II)Activates K+ channel; inactivates Ca2+ channels
By Go
188
(II)Activates phospholipase C-B
a and By Go
189
(II)activates cyclic GMP phosphodiesterase in vertebrate rod receptors
a Gt (transducin)
190
(III) Activates phospholipase C-B
a Gq
191
(IV) Activates Rho family monomeric GTPase (via Rho-GEF) to regulate the actin cytoskeleton
a G12/13
192
-Gaseous signaling mediator that passes between cells
- hydrophobic, small, readily pass across the plasma membrane
nitric oxide (NO)
193
Function of nitric oxide
relax smooth muscles in the walss of blood vessels
194
_______ stimulates NO synthesis
acetylcholine
195
NO diffuses out of the cell into neighboring
smooth muscle cells
196
____________ depends on relay chains of intracellular signaling proteins and second messengers for amplifying cascade of ______
GPCRs; stimulatory signals
197
GPCRs 3 modes of adaptation
1. receptor sequestration
2. receptor down- regulation
3. receptor inactivation
198
they are temporarily moved to the interior of the cell so that they no loger have acces to their ligand
receptor sequestration
199
destroyed in lysosomes after internalization
receptor down-regulation
200
they become altered so that they can no longer interact with G proteins
receptor inactivation
201
- depend on their phosphorylation by GPCR kinases
- arrestin desensitization
receptor inactivation
202
prevents the activated receptor from interacting with G proteins
