5. Cell Signaling Flashcards
(161 cards)
1
Q
principles of cell signalling
A
mechanisms for responding to
physical and chemical changes in
their environment
2
Q
3 principles of cell signaling
A
- exchange of mating factors
- mating
- new a cell
3
Q
4 protein process of cell signaling
A
- extracellular signal molecule
- receptor protein
- intracellular signaling proteins
- effector proteins
4
Q
3 effector proteins
A
- metabolic enzyme
- transcription regulatory protein
- cytoskeletal protein
5
Q
Effector protein that altered cell shape or movement
A
cytoskeletal protein
6
Q
Effector protein that altered gene expression
A
transcription regulatory protein
7
Q
Effector protein that altered metabolism
A
metabolic enzyme
8
Q
cells produce signals that they
themselves respond to
A
autocrine signalling
9
Q
performed by neurons that
transmit signals electrically along their
axons and release neurotransmitters at
synapses, which are often located far
away from the neuronal cell body.
A
synaptic signalling
10
Q
depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body
A
endocrine signalling
11
Q
depends on local mediators that are
released into the extracellular space and
act on neighboring cells.
A
paracrine signalling
12
Q
2 mechanisms of receptors
A
cell-surface receptors
intracellular receptors
13
Q
communication between cells in multicellular organisms is mediated by
A
extracellular signal molecules
14
Q
extracellular signal molecule
A
ligand
15
Q
Reception of the signals depends on ___ at the cell surface, which bind the signal molecule
A
receptor proteins
16
Q
they process the signal inside the
receiving cell and distributing it to the appropriate intracellular targets
A
intracellular signaling proteins
17
Q
the targets that lie at the end of signalling pathways are generally. altered in some way by the incoming signal and implement the appropriate change in cell behavior.
A
effector proteins
18
Q
he fundamental features of cell signaling have been conserved throughout the
evolution of the _____
A
eukaryotes
19
Q
Expound the cell signaling in budding yeast
A
the response to mating factor depends on
* cell-surface receptor proteins
* intracellular GTP-binding proteins
* protein kinases
20
Q
requires cells to be in direct membrane-membrane contact
A
Contact-dependent signaling
21
Q
they are high specificity of binding site of receptors
A
target cells
22
Q
Their extracellular domains may be released from the signaling cell’s surface by proteolytic cleavage and then act at a distance.
A
Transmembrane signal proteins
23
Q
the target cell responds by means of a _____
A
receptor
24
Q
binds the signal molecule and then initiates a response in the
target cell.
A
receptor
25
The binding site of the receptor has a complex structure that is shaped
to recognize the signal molecule with _____
high specificity
26
Binding of ECS Molecules: Most signal molecules are hydrophilic and are therefore unable to cross the target cell’s plasma membrane directly
cell-surface receptors
27
Some small signal molecules,
by contrast, diffuse across the plasma membrane and bind to receptor proteins inside the target cell
intracellular receptors
28
each cell is programmed to respond to ____ of extracellular signals
specific combinations
29
cell responds to the signals ____
selectively
30
if deprived of appropriate survival signals, a cell will undergo a form of cell suicide known as
apoptosis
31
a signal molecule often has __ __ on different types of target cell
different effects
32
the differences of the extracellular signal. why?
it simply induces the cell to respond according to its predetermined state, which depends on the cell’s developmental history and the specific genes it expresses.
33
three major classes of cell-surface receptor proteins
ion-channel coupled receptors
g-protein coupled receptors
enzyme-coupled receptors
34
converting an extracellular
ligand-binding event into
intracellular signals that alter the
behaviour of the target cell
signal transducers
35
Ion-channel-coupled receptors, also known as __ or __
transmitter-gated ion channels or ionotropic receptors
36
involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells
ion-channel-coupled receptors
37
Ion-channel-coupled receptors is mediated by _______
neurotransmitters opening or closing an ion channel
38
what happens in ion-channel receptors?
* transmitter-gated ion
channels or ionotropic
receptors
* electrically excitable cells
* neurotransmitters
39
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
40
mediates the interaction between the activated receptor and this target protein
trimeric GTP-binding protein (G protein)
41
how does G-proteins work?
can change the concentration of small intracellular signaling molecules OR change ion permeability
42
function as enzymes or associate directly with enzymes that they activate
enzyme-coupled receptors
43
enzyme-coupled receptors (5)
* function as enzymes or associated directly with enzymes
* single-pass transmembrane proteins
* ligand-binding outside the cell
* enzyme-binding site inside
* protein kinases
44
intracellular signaling molecules are small chemicals, which are often
called _______
second messengers
45
generated in large amounts in response to receptor activation and diffuses away from their source, spreading the signal to other parts of the cell.
second messengers
46
When they receive a signal, they switch from an inactive to an
active state, until another process switches them off, returning them to their inactive state.
molecular switches
47
phosphorylation enzymes
protein kinase - on
protein phosphatase - off
48
2 types of protein kinase
serine/threonine kinase
tyrosine kinases
49
A protein kinase covalently adds a phosphate from ATP to the signaling protein, and a protein phosphatase removes the phosphate.
phosphorylation
50
induced to exchange its
bound GDP for GTP activates the protein; the protein then inactivates itself by hydrolyzing its bound GTP to GDP.
GTP-binding proteins
51
switches of GTP-binding proteins
GTP - on
GDP - off
52
2 types of GTP-binding proteins
trimeric GTP-binding proteins
monomeric GTP-binding
proteins
53
help relay signals from G-protein-coupled receptors that activate them
G-proteins
54
help relay signals from many classes of cell-surface receptors
small monomeric GTPases
55
drive the proteins into an “off” state by increasing the rate of hydrolysis of bound GTP
GTPase-activating proteins (GAPs)
56
activate GTP-binding proteins by promoting the release of bound GDP, which allows a new GTP to bind.
guanine nucleotide exchange factors (GEFs)
57
a sequence of two inhibitory steps can have the same effect as one activating step
double-negative activation
58
an activated intracellular signalling molecule should interact only with the appropriate __ __
downstream targets
59
2 characteristics of complementary surfaces
high affinity and specificity
60
The ability of downstream target proteins to simply ignore such signals respond only when the ___
upstream signal reaches a high concentration or activity
level
61
involves scaffold proteins
localization
62
holds the protein in close proximity;
interact at high local concentration;
sequentially activated rapidly
signaling complexes
63
phosphorylated cytoplasmic tail of the receptor serve as
Docking sites
64
which bring together groups of interacting signaling proteins into signaling complexes, often before a signal has been received
Localization (scaffold proteins)
65
they can interact at high local concentrations and be sequentially activated rapidly, efficiently, and selectively in response to an appropriate extracellular signal
Scaffold proteins
66
holds the protein in proximity; interact at high local concentration; sequentially activated rapidly
Signaling complexes
67
form only transiently in response; around a receptor
Signaling complexes
68
production of _____which recruit specific intracellular signaling proteins
Phosphoinositides
69
Specialized behaviors that produce appropriate for the cell function that system controls (7)
1. Response timing
2. Sensitivity to extracellular signals
3. Dynamic range
4. Persistence
5. Signal processing
6. Integration
7. Coordination
70
Number or affinity; amplification
Sensitivity to extracellular signals
71
Responsiveness
Dynamic range
72
Transient response; prolonged or permanent
Persistence
73
Switchlike response; oscillatory response
Signal processing
74
Multiple inputs
Integration
75
Multiple responses
Coordination
76
speed of response depends on the nature of _____
intracellular signaling molecules
77
Signaling if only changes in proteins already present in the cell (altered protein function)
Occurs rapidly: allosteric change in a neurotransmitter-gated ion channel
77
changes in gene expression and the synthesis of new proteins (altered protein synthesis)
Occurs in minutes or hours, regardless of mode of signal delivery
78
response fades when a _____
signal ceases
79
2 types of abrupt responses when signal concentration rises beyond some threshold value
Sigmoidal
Discontinuous or all-or-none
80
low concentrations of stimulus do not have much effect, but then the response rises steeply and continuously at intermediate stimulus levels
Sigmoidal response
81
response switches on completely (and often irreversibly) when the signal reaches some threshold concentration
Discontinuous or all-or-none
82
Smoothly graded response
hyperbolic
83
the output of a process acts back to regulate that same process
feedback loops
84
output stimulates its own production
Positive feedback
84
output inhibits its own production
Negative feedback
85
* muscle-cell specification
* all-or-none responses
* all cells in a population do not respond identically to the same concentration of extracellular signal
Positive feedback
85
steepen the response – sigmoidal or all-or-none response
Positive feedback
86
Self-sustaining, bistable, can have switches
Positive feedback
87
counteracts the effect of a stimulus
* limits the level of the response
Negative feedback
87
In positive feedback, _____ can induce long
term changes in cells and their progeny that can persist for the lifetime of the
organism.
transient extracellular signal
88
Delay in negative feedback
Oscillations
89
respond to changes in the concentration of an extracellular signal molecule
Adaptations
90
cells and organisms can detect the same percentage of change in a signal over a wide range of stimulus strengths
Adaptation or desensitization
91
Some ways that the cell may adapt
Receptor sequestration
Down-regulation
Inactivation
Inactivation of signaling protein
Production of inhibitory protein
92
largest family of cell-surface receptors, they mediate most responses to signals from the external world, as well as signals from other cells, including hormones, neurotransmitters, and local mediators.
G-protein-coupled receptors
93
What senses depend on G-proteins?
Sight, smell. Taste
93
Describe the structure of G-protein-coupled receptors
a single polypeptide chain that threads back and forth across the lipid bilayer seven times, forming a cylindrical structure
93
it function is to couple the receptor to enzymes or ion channels in the membrane.
trimeric GTP-binding protein (G protein)
94
3 protein subunits of G proteins
a, B, and y
94
GTPase and becomes inactive when it hydrolyzes its bound GTP to GDP
GTPase Activating Proteins
94
When a subunit has GDP bound and the G protein is inactive
Unstimulated and inactivated
95
Activation of GPCR
acts like guanine nucleotide
exchange factor (GEF)
96
Cyclic AMP is synthesized from ATP by an enzyme called
Adenylyl cyclase
96
Sequence of signaling through G-protein-coupled receptors
Α subunit release its bound GDP →
binding of GTP →
conformational changes →
dissociation of the GTP bound Gα subunit from the Gβγ pair
96
acts as a second messenger in some signaling pathways
Cyclic AMP
96
c-AMP is continuously destroyed by
cyclic AMP phosphodiesterases
97
stimulatory G protein activates adenylyl cyclase
Gs (stimulatory)
97
What regulate the production of cyclic AMP
G-proteins
97
What happens in pertussis toxin (whooping cough)
ADP ribosylation of the α subunit of Gi
98
What happens in cholera toxin?
ADP ribosylation that alters the Gs α subunit
98
Inhibitory of adenylyl cyclase
Gi (inhibitory)
98
cAMP exerts its effects mainly by activating what? _____
cyclic-AMP dependent protein kinase (PKA)
98
Adrenal cortex: Cortisol secretion
Adrenocorticotrophic hormone (ACTH)
98
Ovary: Progesterone secretion
Luteinizing hormone (LH)
99
Thyroid gland: thyroid hormone synthesis and secretion
Thyroid-stimulating hormone (TSH)
100
Muscle: Glycogen breakdown
Adrenaline
101
Bone resorption
Parathormone
101
A specific transcription regulator called ______ recognizes this sequence
CRE-binding (CREB) protein
101
Increase in heart rate and force of contraction
Adrenalin
101
cAMP activates the gene that encodes the hormone ____
Somatostatin
101
Glycogen breakdown in liver
glucagon
101
[PI(4,5) P2]
phosphatidylinositol 4,5-bisphosphate
101
Water absorption in kidney
Vasopressin
101
PKA inactive state:
two catalytic subunits and two regulatory subunits
101
PKA phosphorylates specific ___ and _____
Serines and threonines on target proteins
101
When PKA is acti vated by cAMP, it phosphorylates CREB on a single serine; phosphorylated CREB then recruits a transcriptional coactivator called
CREB-binding protein (CBP)
101
The activated phospholipase then cleaves the PI(4,5)P2 to generate two products:
inositol 1,4,5-trisphosphate (IP3) and diacylglycerol
101
PKA activated state:
Released catalytic subunits
101
The regulatory region of the somatostatin gene contains a short cis-regulatory sequence
cyclic AMP response element (CRE)
101
CREB can transform a ___ cAMP signal into a ___-term change in a cell
Short, long
101
What does diacyglyerol activates?
activate protein kinase C (PKC)
101
Acts on inositol phospholipid signaling pathway
phospholipase C-β (PLCβ)
101
G protein called ___ activates GEF (___) that activates a monomeric GTPase (Rho family) which regulates the actin cytoskeleton
G12
guanine nucleotide exchange factor
101
Activates phospholipase C-B
Protein Gq
101
Cite the process of IP3 activation
endoplasmic reticulum IP3-gated Ca2+-release channels (IP3 receptors) increases concentration of Ca2+ in the cytosol
101
What are the specific GPCRs to recognize odors which acts through cAMP
Olfactory receptors
101
What senses depend on GPCRs that regulate ion channels?
Smell and vision
102
directly activate or inactivate ion channels in the plasma membrane of the target cell, thereby altering the ion permeability— and hence the electrical excitability—of the membrane.
G12 protein
102
Example of G12 protein
Acetylcholine
102
They activate an olfactory-specific G protein (known as Golf), which in turn activates ______
adenylyl cyclase
102
How many olf receptors in human?
350
102
chemical signals detected in a different part of the nose that are used in communication between members of the same species
Pheromones
102
receptor activation stimulated by light causes ___ in the level of cyclic nucleotide
A fall
102
stack of discs; contains cyclic-GMP-gated cation channels
phototransduction apparatus
102
What is the crucial in vision? (clue: aside from cAMP)
Cyclic GMP
102
continuous rapid synthesis
Guanylyl cyclase
102
rapid degradation (by what enzyme?) controls the concentration of cyclic GMP in the cytosol
cyclic GMP phosphodiesterase
102
responsible for noncolor vision in dim light
Rod photoreceptors (rods)
102
responsible for color vision in bright light
cone photoreceptors (cones)
102
___ bound to these channels keeps the rhodopsin open in the dark
Cyclic GMP
102
In the light, it happens due to decreases the cyclic GMP conc. and closes the cation channel
Hyperpolarization
102
It phosphorylates the cytosolic tail of activated rhodopsin on multiple serines
rhodopsin kinase (RK)
102
activated by a photon of light
Rhodopsin
102
The isomerization of all-trans retinal alters PROCESS
conformation of transducin (Gt) → activate the cyclic GMP phosphodiesterase →hydrolyzes cyclic GMP → GMP levels fall
102
This hormone relaxes smooth muscles in the walls of blood vessels
Nitric oxide (NO)
102
Inhibits rhodopsin kinase (RK)
Arrestin
103
What stimulates NO synthesis?
acetylcholine
104
diffuses out of the cell into neighboring smooth muscle cells
Nitric Oxide (NO)
105
GPCRs 3 modes of adaptation
1. receptor sequestration
2. receptor down-regulation
3. receptor inactivation
106
* prevents the activated receptor from interacting with G proteins * adaptor protein
Arrestin desensitization
