Cell bio- cell signaling Flashcards
(263 cards)
1
Q
What are the 4 categories of chemical signaling?
A
Free diffusion between cells- adjacent cells or distant cells
cell signals to itself
cell-to-cell contact-mediated signaling
2
Q
What are two regulating roles of extracellular signalling molecules?
A
regulate interaction between cells
regulate physiology and development in multi-cellular organisms
3
Q
What are 5 effects of cell signaling?
A
coordinate the aggregation or movement of cells
initiate and control differentiation under certain environment conditions
alter gene expression
influence the composition of intracellular and extracellular fluids
contribute to nerve conduction
4
Q
What are three things that are controlled by the effects of cell signaling?
A
metabolic processes within cells
growth of tissues
synthesis and secretion of proteins
5
Q
What are 5 different types of signals?
A
membrane-anchored and secreted proteins and peptides
small lipophilic molecules
small hydrophilic molecules derived from AA
gases
physical stimuli
6
Q
What are 4 receptor-binding signal molecules?
A
Cytokines- growth factors
neurotransmitters
hormones
nitric oxide
7
Q
What 4 things does target cell response depend on?
A
signals that are present
receptors that the target cell expresses on cell surface or intracellularly
signaling cascades
intracellular targets
8
Q
what is the definition of a ligand?
A
a molecule which binds to a receptor
9
Q
What are the three steps for detecting a signal?
A
Reception- signaling molecule binds to its receptor
transduction- binding alters the shape or activity of the receptor
response- ligand binding triggers a change inside of the cell
10
Q
what are the two types of ligands?
A
those that enter the cell- bind to transmembrane/intracellular receptors
bind outside the cell- bind to membrane bound receptors
11
Q
What physical properties will ligands have in order to enter the cell? (2)
A
small lipid soluble (hydrophobic)
12
Q
What is a key role for intracellular ligands?
A
to activate a signaling pathway in the smooth muscle surrounding blood vessels- causes the muscle to relax and allows the blood vessel to expand (dilate)
13
Q
What are characteristics of extracellular ligands? (2)
A
water-soluble
polar or charged
14
Q
what type of ligand is the largest and most diverse class of water-soluble ligands?
A
peptide (protein) ligands
15
Q
what are 3 examples of extracellular ligands?
A
growth factors
hormones (insulin)
some neurotransmitters
16
Q
What are 4 types of neurotransmitters and examples?
A
(neuro)peptides= oxytocin, endorphin
small, hydrophilic organic molecules, monoamines= dopamine
standard AA= glutamate and glycine
modified or non-standard AA
17
Q
What are two other types of signal molecules?
A
light- phototransduction
pressure- mechanotransduction
18
Q
What are two types of receptors?
A
internal
cell-surface
19
Q
Where are internal receptors found?
A
in the cytoplasm of the cell
20
Q
What does ligand-binding cause to the internal receptor?
A
conformational changes that exposes a DNA-binding site on the protein
21
Q
what are the three stages of the ligand-receptor complex?
A
moves into the nucleus
binds to specific regulatory regions of the chromosomal DNA
promotes the initiation of transcription and thus gene expression
22
Q
What signal do cell-surface receptors trigger?
A
transduction- an extracellular signal is converted into an intercellular signal
23
Q
What are three other names for cell-surface receptors
A
transmembrane receptors
cell-specific proteins
markers
24
Q
what are the three main components to cell-surface receptors?
A
an external ligand-binding domain
a hydrophobic membrane-spanning region
an intracellular domain inside the cell
25
What type of cell signaling is autocrine signaling?
cell signaling to itself or a similar cell
26
What are auntocrine signals produced by?
signaling cells that can also bind to the ligand that is released
27
When is autocrine signaling commonly used?
early development to ensure that cells develop into the correct tissues and take on the proper function
28
What two processes is autocrine signaling also involved in?
regulating pain and inflammatory responses
| programmed cell death (apoptosis)
29
How to T lymphocytes use autocrine signaling?
to respond to antigentic stimulation by secreting a growth factor that drives its own proliferation= amplifying the immune response
30
What happens when abnormal autocrine signaling occurs?
uncontrolled growth of cells (cancer)- if the cell produces a growth factor and can respond to it, it will continuously drive its own unregulated proliferation
31
What type of signaling is endocrine signaling?
signals from distant cells
32
What are the ligands released in endocrine signaling called?
hormones
33
What kind of a response does endocrine signaling produce?
slower response, but has a longer-lasting effect
34
how are hormones produced and sent to target cells?
produced in one part of the body but affect other body regions by traveling via the bloodstream. They get diluted and are present in low concentrations when acting on target cells
35
What type of signaling is paracrine signaling?
the release of chemical messengers between cells that are near each other
36
what is the characteristic of ligands used in paracrine signaling?
they can diffuse through the space between the cells
37
when is paracrine signaling important?
during development. allows some group of cells to instruct a neighboring group of cells what cellular identity to take on
38
What is an example of paracrine signaling?
synaptic signaling- allows nerve cells to transmit signals
39
what is the four stages of synaptic signaling?
sending cell= presynaptic
neurotransmitter is released in the synapse
post synaptic cell= receiving cell
pesonse= nerve conduction
40
what call structure is used in cell-to-cell contact-mediated signaling?
gap junctions
41
how is cell-cell contact-mediated signaling different than other cell-cell connections
triggers signaling, rather than structural properties
42
what are three types of direct signaling across gap junctions?
gap junctions in animals
plasmodesmata in plants
water-filled channels
43
What does ligand specificity in gap junction channels ensure?
that the cells remain independent but allows cells to transmit signals quickly and easily
44
What does direct signaling across gap junctions allow?
a group of cells to coordinate their response to a signal that only one of them may have received
45
What is an example of a ligand that can act in multiple types of cell-to-cell signaling?
small AA derivatives (epinephrine)
neurotransmitters= paracrine signaling
systemic hormones= endocrine signaling
46
When does maximum cellular response occur?
when saturation between ligand and receptor is reached= all receptor binding sites for that one ligand are occupied
47
what is saturation a consequence of?
the finite number of receptors for a specific ligand
48
in animals, what junction permits the free passage of ions and small molecules between neighboring cells?
gap junctions
49
what type of signaling consists of free diffusion of chemical signals between adjacent cells (within interstitial space?)
Paracrine
50
what is an example of ligan-binding and effector specificity with different functions of the same receptor?
acetylcholine receptors- found on surface of striated muscle cells, heart muscle cells and pancreatic acinar cells.
51
What is the process of Acetylcholine receptors?
relase of acetylcholine from neuron adjacent to a striated muscle cell triggers contraction
release adjacent to heart muscle slows the rate of contraction
release adjacent to pancreatic acinar cell triggers exocytosis or secretory granules that contail digestive enzymes
52
what is an example of a ligand-binding and effector specificity with different receptors having the same function?
activation or epinephrine or glucagon receptors on liver cells
53
what is the process of epinephrine and glucagon receptors?
binding of ligand induces synthesis of cyclic AMP- regulates various metabolic functions
54
What are the four major classes of cell-surface receptors?
g protein-coupled receptors
ion-channel receptors
tyrosine kinase-linked receptors
receptors with intrinsic activity
55
what three mechanisms does cell-surface receptors use to transform external signals into internal ones?
protein action
ion channel opening
enzyme activation
56
What 2 characteristics of signaling molecules make them require cell-surface receptors?
they are too big or too charged to cross a plasma membrane
57
what is another name for ion-channel receptors
ligand-gated ion-channel receptors
58
what are the three steps of ion-channel receptors?
ligand binding changes the conformation of the receptor
allows specific ions to pass through it
ion movement alter the electric potential across the cell membrane
59
what ions are allowed to pass through ion-channel receptors? (5)
```
Na+
Ca+
Mg+
K+
H+
```
60
What cells are most likely to have ion-channel receptors?
nerve cells
61
What are the ligands for ion-channel receptors? (2)
small AA neurotransmitters (glutamate) and acetylcholine
62
What is the result after ligands binds to receptors with intrinsic catalytic activity
receptors directly convert GMP to cGTP or ATP into cAMP to trigger cell response
63
what is an example of a receptor with intrinsic enzymatic activity?
receptor for Atrial Naturetic Protein (ANP)
64
what is the role of ANP and receptors with intrinsic enzymatic activity?
causes a reduction in blood volume, which causes a reduction in cardiac output and systemic blood pressure
lipoysis is increased and renal sodium re-absorption is decreased
65
what is an example of an enzymatic cell-surface receptor?
tyrosine-kinase linked receptors
66
what does tyrosine kinase linked receptors lack and what does it binding to a ligand do?
lacks intrinsic catalytic activity
ligand binding stimulates formation of a dimeric receptor, which interacts with and activates one or more cytosolic protein tyrosine kinases
67
what is another name for tyrosine kinase linked receptors?
cytokine receptor superfamily
68
what are three examples of enzyme linked receptors?
cytokines, interferons, human growth factor
69
what is one of the largest family of cell surface receptors?
G protein coupled receptors
70
what does ligand binding to a g protein coupled receptor activate?
a signal transduction cascade starting with release of a G protein, which activates or inhibits an enzyme
71
what does the release of a g protein generate?
a specific secondary messenger or modulates an ion channel, causing a change in membrane potential
72
what is the structure of g protein coupled receptors? (4)
7 hydrophobic transmembrane segments
an extracellular amino terminus
an intracellular carboxyl terminus 7-trandmembrane receptor
coupled to inactive g protein bound to a trimeric subunit (alpha, beta, gamma)
73
What are three functions of g protein coupled receptors?
structural diversity of the natural GPCR ligands
regulate a large range of physiological functions
drug discovery and design
74
structural diversity of natural GPCR ligands (4)
subatomic particles (photons)
ions (H+ and Ca2+)
small organic molecules
peptides and proteins
75
4 physiological functions that are regulated by GPCR
hormone secretion in pancreas/ gluconeogenesis in liver
platelet-mediated blood clotting (thrombin)
blood pressure regulation (angotensis 2/ epinephrine)
mood (serotonin)
76
4 examples of GPCR
epinephrine
serotonin
angiotensin 2
glucagon
77
importance of drug discovery and design of GPCR
1/3-1/2 drugs act by binding to GPCRs
multiple actions in signal transduction pathway
multiple physiological functions
78
what are the two main differences between receptor categories?
speed of effect and duration of effect
79
what are the 4 diverging effects of a cascade of secondary messenger systems
opening another channel via an internal binding site
increasing or decreasing transcription
protein modifications, including phosphorylation
downstream effects
80
what is the purpose of short-term signaling?
to allow organisms to be able to respond instantly to many changes in their internal or external environment
81
what 2 molecules mediate short-term signaling?
peptide hormones and catecholamines (epinephrine, norepinephrine and dopamine)
82
how long does peptide hormones last in the blood and why?
seconds-minutes. they are degraded by blood and tissue proteases
83
how long does catacholamines last in the blood and why?
they are rapidly inactivated by different enzymes or taken up by specific cells
84
how long do the actions of signaling molecules on target cells in short-term signaling last and why?
seconds-minutes before the responses are terminated by ligand degradation
85
what is an example of ionotropic receptors?
ion-gated channels/receptors
86
what are 3 examples of metabotropic receptors?
g protein- coupled receptors
tyrosine kinase-linked receptors
receptors with intrinsic enzymatic activity
87
how do cells respond to signals?
once a receptor protein recieves a signal, it undergoes a conformational changes, which launches a series of reactions within the cell= signal transduction cascades, which amplify the message= produces multiple intracellular signals for every one bound receptor
88
what are 3 characteristics of ionotropic receptors?
transmembrane molecules that can open or close a channel
allows different kinds of cations to travel in and out of the cell
closed until a ligand binds to the receptor
89
what are the 4 domains of ionotropic receptors?
extracellular amino-terminal (ATD)
extracellular ligand-binding (LBD)
four transmembrane (TMD)
intracellular carboxyl-terminal (CTD)
90
what is an example of ionotropic receptors?
ionotropic glutamate receptors= ligand-gated nonselective cation channels
91
what are the three functions of ionotropic glutamate receptors?
allow the flow of K,Na, and Ca in response to glutamate binding
mediate the majority of excitatory neurotransmission within the brain
upon binding, glutamate will stimulate direct action of the central pore of the ion channel
92
Where are ionotropic glutamate receptors found? (2)
pre and post synaptic cell membranes, primarily within the CNS
93
What are the three subfamilies of ionotropic glutamate receptors?
AMPA
NMPA
kainate
94
NMDA receptor function
internal binding site for a Mg ion, creates a voltage-dependent block, which is removed by outward flow of positive current
95
What are NMDA receptors permeable to and what is its role?
Ca ions- plays an important role in he nervous system and has been linked to gene regulation
96
what does the flow of Ca through NMDA receptors cause?
log-term synaptic action by transducing signaling cascades and regulating gene expression
97
What do metabotropic receptors lack and how to they conduct cell signals?
lack a channel that open or closes
| conducts cell signals through signaling cascades which involve second messengers and/or phosphorylation
98
3 main characteristics of ionotropic receptors that make it different than metabotropic receptors
act very quickly
change shape and allow ions to flow in when a ligand is bound to it
the ligand is displaced/degraded quickly, causing the channel to close back
99
4 main characteristics of metabotropic receptors that make it different than ionotropic receptors
take longer to trigger a response
depends on the number of steps in the signaling cascade
once a receptor is activated, signaling cascade is initiated
phosphorylation will activate a number of enzymes
100
what is an example of a metabotropic receptor
MAPK pathway= a series or protein reactions in the cell.
101
how does the MAPK pathway start?
starts when a signaling molecule (EGF) binds to the receptor on the cell surface
102
whatactivates tyrosine kinase-linked receptor, and what happens afterwards?
binding of EGD activates the tyrosine kinase activity in the cytoplasmic domain of the receptor. the pathway includes many proteins and phosphorylations.
103
what is the end step of the tyrosine kinase-linked receptor and what does it signal?
end step= transcription factor phosphorylation
| signal ends which gene expression/protein production and a cellular response
104
what are 2 other examples of signaling cascade receptors with intrinsic enzymatic activity?
MAP kinase pathway= indirect connection between cell surface and nucleus
Alternative pathway= JAK/STAT pathway= immediate connection between protein-tyrosine kinases and transcription factors
105
What does tyrosine phosphorylation affect?
directly affects transcription factor localization and function
106
What do metabotropic receptors involve and what to they result in?
incolve second messengers ( g protein coupled receptors)
| these messengers can travel throughout the cell and result in a much wider range of responses
107
what is the definition of secondary messenger
a chemical whose function is to go and activate other particles
108
What are three types of membrane receptors that the ligand activated?
ion-channel receptor
G-protein coupled receptor
enzymatic/enzyme linked receptor
109
Increase in intracellular concentration of second messengers following hormone binding triggers a rapid alteration in the activity of what? (2)
one or more enzymes
| nonenzymatic proteins= transcription factor
110
what are three metabolic functions controlled by hormone-induced second messengers?
uptake and utilization of glucose
storage and mobilization of fat
secretion of cellular products
111
what are 4 cellular functions that are controlled by intracellular molecules?
proliferation
differentiation
cell survival
cell migration
112
what 3 actions cause a intracellular signal to stop?
removal (degredation) or the ligand
removal (degredation) or the second messenger
inactivation of the ligand-binding receptor
113
how does intracellular signaling control cell functions?
by regulating the transcription of specific genes
114
What does phosporylation allow in cell signaling?
intricate control of protein function
115
where are phosphate groups added to on the protein and what may the protein become after its phosphorylated?
added to multiple sites in a single protein
| the protein may be the substrate for multiple kinases and phosphates
116
How does the addition of phosphate groups affect the enzyme? (2)
controls the activity of enzymes involved in intracellular signaling pathways
causes a conformational change , which either activated or inhibits the enzyme activity
117
what is the role of protein phosphatases?
remove the phosphate groups from the enzymes= reverse the effect on enzymatic activity
118
What are two additional factors that affect the catalytic activities of kinases
direct binding to other proteins
| changed in the levels of various second messengers
119
where are two places that kinases can be found?
as part of the receptor
| in the cytosol or associated with the plasma membrane
120
what are two mechanisms categories of PKA?
direct protein phosphorylation
| protein synthesis
121
How does PKA affect proteins through direct protein phosphorylation?
directly increases or decreases the activity of protein
122
How does PKA affect proteins through protein synthesis?
directly activates CREB (non enzymatic protein= transcription factor) which binds the response element
123
What does PKA activating the CREB alter?
gene transcription= synthesis of the protein
124
Is the protein synthesis a quick or slow process?
slow, takes hours
125
what is PKC known for?
long-term activation
| remains activated after the original activation signals of the calcium wave is gone
126
How does PKC activate enzymes
by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions
127
what happens to PKC enzymes after it is activated
they are trnaslocated to the plasma membrane by RACK proteins (binding proteins)
128
where to activated RTKs become autophosphorylated?
on multibple specific intracellular tyrosine residues
129
What are 4 types of second messengers?
cAMP
cGMP
phospholipids
Ca2+
130
what is cAMP a derivative of?
ATP
131
where is cAMP present in and what does it convey?
intracellular signal transduction in many different organisms
132
how is cGMP best characterized in animal cells?
visual reception in vertebrate eye
133
Where are phospholipids and Ca2+ secondary molecules activated?
downstream of both G protein-coupled receptors and protein-tyrosine kinases (in the Cytosol)
134
where are two less common second messengers ?
1,2-diacylglycerol (DAG)
| inositol 1,4,5-trisphosphate (IP#3)
135
Ligand binding to many cell-surface, metabrotrophic receptors leads to what?
a short-lived increase in the concentration of second messengers
136
what is the role of second messengers?
initiate and coordinate the intracellular signaling pathways
137
what does cAMP respond to in animal cells? (2)
variety of hormones and odorants
138
what molecule mediates most actions of cAMP?
PKA
139
What is the structure of the inactive form of PKA?
tetamer: 2 catalytic and 2 regulatory subunits
140
How does cAMP signal the breakdown of glycogen?
cAMP binds to the regulatory subunits of PKA, causes dissociation from catalytic subunits= free catalytic subunits are enzymatically active, which then phosphorylates serine residues on their target proteins
141
What are the two key target enzymes or PKA?
another protein kinase= phosphorylase kinase
| glycogen synthase
142
What does phosphorylase kinase do and what is the result?
phosphorylates glycogen phosphorylase, which then catalyzes and breakdown of glycogen to glucose
143
What does phosphorylation of glygocen synthase by PKA result in?
inhibits enzymatic activity= blocks further glycogen production
144
What does the elevation of cAMP and activation of PKA do?
blocks further glycogen synthesis and stimulates glycogen breakdown
145
in animal cells, increase in CAMP activates what?
transcription of specific target genes
146
what is the regulatory sequence that is in genes affected by increase in cAMP?
cAMP response element
147
What is the function of the genes in the cAMP response element?
signal is carried from teh cytoplasm to the nucleus by catalytic subunits of PKA
148
PKA phosphorylates CREB, which leads to what?
activation of cAMP-inducible genes
149
How does cAMP stop signaling?
it is degraded by the enzyme phosphodiesterase
150
How does cAMP function when sensing smells?
directly regulates ion channels without protein phosphorylation
151
what are the steps of sensing smells? (4)
ordorant molecules bind to receptors in the nose (g proteins coupled receptors)
Stimulates adenylyl cyclase= increased intracellular cAMP
cAMP directly opens Na channels in the plasma membrane
causes membrane depolarization and initiation of nerve impulse
152
What three systems do cGMP regulate?
ion channel conductance
glycogenolysis
cellular apoptosis
153
What funciton in the body is affected my cGMP and an example?
relaxed smooth muscle tissues
| blood vessels= relaxation of smooth muscles leads to vasodialation and increased blood flow
154
What is cGMP a second messenger of in the eye?
phototransduction
155
what is the photoreceptor in the eye an how is it activated?
g protein-coupled receptor= rhodopsin
| activated as a result to absorption of light, inducing a conformational change in rhodopsin
156
How is the signal from cGMP stopped?
Rhodopsin activates the G protein Transducin
alpha subunit of transducin stimulated the activity of cGMP phosphodiesterase, which leads to a decrease in the intracellular level of cGMP, which causes Na channels to close
157
What does the hydrolysis of PIP2 yield and what are their functions? (2)
two phospholipid secondary messengers:
diacylglycerol= activate PKC
IP3= mobilizes Ca2+ from intracellular stores
158
What does Ca2+ activate after it is released from IP3?
protein-serine/threonine kinases in the PKC family
159
What does increased levels of Ca2+ activate?
a variety of target proteins, including Ca2+/calmodulin-dependent protein kinases
160
What are two methods of increasing levels of cytosolic Ca2+ in electrically excitable cells (nerve and muscle)?
voltage-gated Ca2+ channels in the plasma membrane
| ryanodine receptors in the ER and sarcoplasmic reticulum
161
what is an example of the role of PKC?
action of phorbol esters= promote growth of tumors in animals
162
what are phorbol esters?
analogs of siacylglycerol
163
how to phorbol esters stimulate PKC?
PKC activates intracellular targets= MAP kinase pathway
| leads to transcription of factor phosphorylation= changes gene expression and stimulates cell proliferation
164
what is the outcome of phosphorylation of PIP2?
PIP3= second messenger
165
what is an example of signal amplification?
epinephrine and glycogen
166
how do epinerphrine and glycogen cause a signal amplification?
each molecule activates a single receptor, which may activate several molecules of G proteins, which can activate many adenylyl cyclases
167
what are three functions of Ca in cell phsiology?
in the cytosol= exert regulatory effects on many enzymes and proteins
act in signal transduction resulting from activation of ion channels
act as a secondary messenger cause by indirect signal transduction pathways (G protein coupled receptors)
168
What two situation causes Ca-mediated signaling?
when the cell is stimulated to release Ca ions from intracellular stores
when Ca enters the cell through plasma membrane ion channels
169
Why is Ca ion concentration maintained at low levels?
Ca ions are actively pumped form the cytosol to:
extracellular space
ER
mitochondria
170
What three molecules maintain Ca level in the cytoplasm?
Ca-permeable channels
transporters
ATPases
171
What are 3 regulating functions of proteins that require Ca?
asesual and sexual development
circadian clock
protein folding
172
what does depletion of Ca from the ER lead to?
Ca ion entry from outside the cell by activation of store-operated channels (SOCs)
173
What is the in-flowing Ca current from stored Ca reserves called?
Ca2+-release-activated Ca2+ current (CRAC)
174
What 2 molecules are involved in Ca concentration regulation
calsium release-activated calcium channel protein1 (orai1)
| STIM1
175
what is the role of STIM1
senses decreased Ca concentrations in the ER, then clusters and relocated near the plasma membrane, where it activates Orai1 via protein-protein interaction
176
what is an imporatnt role of Orai channels?
activation of T-lymphocytes
177
what does a mutation of the gene Orai1 cause?
loss of function= severe combined immunodeficiency (SCID)
178
Ca signaling example- in electrically non-excitable cells
Ca influx is essential for regulating a host kinetically distinct processes
179
what 5 processes are regulated by Ca in non-excitable cells?
```
exocytosis
enzyme control
gene regulation
cell growth and proliferation
apoptosis
```
180
What are two major means of signal transduction of Ca?
SOC-mediated Ca regulation and CRAC
181
Ca signaling examples- membrane potential
altered from the movement of Ca ions from extracellular to intracellular compartment
in heart= plateau phase of ventricular contraction= maintains depolarization of the heart
182
Ca signaling examples- neuronal synaptic transmission
through ion channels
antigen stimulation of immune cells triggers Ca entry through CRAC channels, promoting the immune response to pathogens by activating the transcription factor NFAT
183
What is the phospholipase C pathway?
signaling pathway that increases cytoplasmic Ca concentration
184
how does the phopholipase C pathway occur?
by opening channels i the ER or the plasma membrane
185
what receptors activate the phospholipase C (PLC) enzyme? (2)
g protein-coupled receptors and recepto tyrosine kinases
186
What are the 5 steps of the PLC pathway?
1. PLC hydrolyses the membrane PIP2 to form IP3 and DAG
2. DAG recruits PKC, attaching it to the plasma membrane
3. IP3 diffuses to the ER and binds to an IP3 receptor
4. the IP3 receptor serves as a Ca channel and releases Ca from the ER
5. the Ca binds to PKC, activating it
187
what are 6 physological roles of Ca as a second messenger?
```
muscle contraction, neuronal transmission as an excitatory synapse
cellular motility (flagella and cilia)
fertilization
cell growth or proliferation
neurogenesis
learning and memory
```
188
what is the result of high levels of cytoplasmic Ca
cause cell to undergo apoptosis
189
What are 4 additional roles of Ca as a second messenger?
regulating enzymatic activity
permeability of ion channels
activity of ion pumps
components of the cytoskeleton
190
what 2 types of molecules stimulate the hydrolysis of PIP2 by PLC?
variety of hormones and growth factors
191
what two downstream signaling pathways do DAG and IP3 stimulate?
PKC and Ca2+ mobilization
192
Increased mitochondria Ca levels are necessary for that?
activation of isocitrate dehydrogenase= a key regulatory enzyme of the Krebs cycle
193
increases in cytocolic and mitochondrial Ca are important for what?
synchronization of neuronal electrical activity with mitochondrial energy metabolism
194
what is the role of the ER in the neuron?
to integrate numerous extracellular and intracellular signals in association with he plasma remembrance
195
what 3 characteristics of the ER allows signals to be carried locally and globally in the cell?
structural characteristics
ability to act as a Ca2+ sink
specific Ca2+ reassembling proteins all work as a system to produce regenerative waves of Ca2+ release
196
What are 4 roles of Ca2+ signals that integrate extracellular and intracellular fluzes?
synaptic plasticity and memory
neurotransmitter release
neuronal excitability
long term changes at the gene transcription level
197
what can ER stress due to Ca signaling cause?
ER associated degradation and autophagy
198
What is calmodulin?
Ca2+ binding protein
199
how is calmodulin activated, and then what does it bind to?
by Ca2+ binding when the concentration of cytosolic Ca2+ increases
binds to a variety of target proteins (protein kinases)
200
what is an example of a Ca2+/calmodulin-dependent protein kinase, and what does it signal and how?
myosin light-chain kinase
| singlas actin-myosin contraction by phosphorylating one of the myosin light channels
201
What is another protein kinase activated by Ca2+/calmodulin?
members of the CaM kinase family
202
what is the role of CaM kinase family?
phosphorylate a number of different proteins, including metabolic enzymes, ion channels and transcription factors
203
What is the role of CaM kinase in the nervous system?
regulated the synthesis and release of neurotransmitters
204
What can CaM kinases regulate and how?
regulate gene expression by phosphorylating transcription factors
205
What is a transcription factor that is phosphorylated by CaM kinase
CREB, phosphorylated at same site by PKA
206
What are 4 examples of the role of calmodulin?
regulation of adenylyl cyclases
phosphodiesterases
regulation of Ca2+ channesl by cAMP
phosphorylating of a number of target proteins by PKA and ca2+/calmodulin
207
what are two ways to inactivate a receptor?
removal of the ligand by degradation or sequestration
| desensitization of the target cell
208
what is an example of degradation of a ligand?
acetylcholine- degraded by enzyme cholinesterase once its released from neuron terminals
209
what does sequestration involve?
binding to proteins other than its normal receptor (decoy receptors or extracellular proteins)
210
what are decoy receptors?
cell surface receptors that bind the ligand. don't convey the signal onward in the pathway
211
what is an example of a decoy receptor?
truncated RTKs that lack the intracellular kinase domain
212
what three ways can desensitization occur?
inactivation of the receptor (blocking its interaction with downstream signaling components)
sequestering the receptor into endocytic vesicles (from which it can be recycled back onto the plasma membrane
degrading the receptor in lysosomes
213
what is an arrestin
a phophorylated receptor bound to a cytosolic protein
214
What are two functions of arrestin
beta-arrestin recruitment, which sterically stops further signaling to G proteins= leads to desensitization
mediate endocytosis of receptors
215
What is another example of desensitization?
induced by binding of a cytosolic protein to the receptor= c-Cbl
216
what is the role of c-Cbl?
binds to phosphotyrosine residues of certain activated RTKs promoting the association of the receptor-Cbl complx with ubiquitin
217
what occurs in endocytosis
the cell engulfs some of the extracellular fluid including material dissolved or suspended in it
218
how is an endosome formed?
a portion of the plasma membrane is invaginated, coated with molecules of the protein clathrin, and pinched off to form a membrane-bounded vesicle
219
What happens to LDL receptors during endocytosis
they are recycled
220
What happens to the LDL particle in endocytosis?
it budds off from the receptor and is degraded by lysosomes to AA and the cholesterol esters are hydrolyzed to FA and cholesterol
221
what is an intracellular receptor?
cytoplasmic receptor that responds to hydrophobic ligands that are able to travel through the plasma membrane
222
what does ligand-binding to intracellular receptors cause?
conformational change that exposes a DNA-binding site on the protein
223
what are the three steps of the ligand-receptor complex and what is the result?
moves into the nucleus
binds to specific regulatory regions of the DNA
promotes initiation of transcription
starts gene expression
224
what is an example of a ligand-receptor complex in intracellular receptors?
nuclear receptors
225
what are nuclear receptors usually held in inactive conformation by what?
inhibitory proteins (chaperones)
226
what are 4 examples of nuclear receptors?
steroid hormones
thyroid hormones
retinoids
vitamin D
227
what can also facilitate nuclear receptors binding to DNA?
association of the receptor-ligand complex with other proteins (coactivator proteins)
228
what is a hormone response element?
a promoter region of the target genes where the receptor-ligand complex binds to
229
what second messenger is produced from the phosphorylaiton of PIP2?
Phosphatidylinositol-3,4,5-triphosphate (PIP3)
230
What 4 mechanisms cause receptor inactivation?
ligand degradation
endocytosis-mediated receptor recycling
degredation of receptors by proteasomes
ligand sequestration by lysosomes
231
true or false: a ligand can bind to several types or receptors?
true
232
true or false: a receptor has high specificity for one ligand?
true
233
true or false: the same ligand-receptor complex can trigger different effects?
true
234
What type of signaling consists of free diffusion of chemical signals between adjacent cells (within intersitial space)?
paracrine
235
what 3 receptors are transmembrane-bound?
ion-channel receptors
g-protein coupled receptors
enzymatic/enzyme-linked receptors
236
in animals, what type of junction permits the free passage of ions and small molecules between neighboring cells?
gap junctions
237
What two junctions are used in plant cells?
plasmodesmata
| gap junctions
238
What two physical properties allow a ligand to diffuse across the plasma membrane?
hydrophobicity
| lipophilicity
239
Given the type of compounds prostaglandins are, they can: (2)
a) bind to intracellular receptors
b) bind to cell-surface receptors
c) cross the plasma membrane of receiving cells
d) initiate a cellular response at the cell surface
b) bind to cell-surface receptors
| d) initiate a cellular response at the cell surface
240
In regards to prostaglandind-mediated signaling, why are prostaglandins not considered hormones? (2)
Prostaglandin signaling is paracrine/autocrine in nature
| they are produced at many different sites in the body
241
Glutamate receptors can by what two types of receptors?
ionotropic and metabotropic
242
How long is the duration of the effect of ligand-gated ion channels?
milliseconds
243
How long is the duration of the effect of nuclear receptors?
hours
244
how long is the duration of the effect of enzyme-linked receptors?
minutes
245
how long is the duration of the effect of GPCR?
minutes
| can be seconds to minutes
246
What are two processes that ionotropic receptors trigger?
short-term/rapid responses
| postsynaptic effects
247
What are three transmembrane receptors?
g-protein coupled receptors
ligand-gated ion channels
protein tyrosine kinase receptors
248
Which of the following is not a secondary messenger?
a) inositol triphosphate
b) G-protein
c) cAMP
d) Ca2+
b) G-protein
249
What are three examples of g protein-coupled receptors?
Rhodopsin
beat-adrenergic receptor
frizzled
250
what common secondary messenger is synthesized from ATP by adenylyl cyclase?
cAMP
251
PKA can mediate its effect in cell signaling by what two methods?
directly activating or inhibiting protein activity
| activating gene expression through transcription factors
252
What two second messengers are produced from the hydrolysis of PIP2?
Diacylglycerol
| Inositol 1,4,5-triphosphate (IP3)
253
What enzyme is responsible for the hydrolysis of DAG and IP3?
Phospholipase C
254
The role of cGMP is best characterized in which type of cell signaling?
phototransduction
255
DAG/IP3 dependent signaling cascades are activated downstream of what 2 receptors?
G-protein coupled receptors
| receptor tyrosine kinase
256
How does the intracellular concentrations of Ca2+ compare to in the extracellular space?
lower intracellular than extracellular
257
true or false: Ca can mediate direct cellular responses as well as acting as a second messenger?
true
258
the effects of Ca as a second messenger are commonly mediated by binding to what?
calmodulin
259
Atrial Naturetic protein binds to what type of receptor?
Enzymatic/enzyme-linked receptor
260
Interferon binds to what type of receptor>
g-protein coupled receptor
261
epinephrine binds to what type of receptor?
g protein coupled receptor
262
glucagon binds to what type of receptor?
g protein coupled receptor
263
Acethylcholine binds to what 2 types of receptor?
Ion-channel receptor
| g protein coupled receptor
