5. Cell Signaling Flashcards
principles of cell signalling
mechanisms for responding to
physical and chemical changes in
their environment
3 principles of cell signaling
- exchange of mating factors
- mating
- new a cell
4 protein process of cell signaling
- extracellular signal molecule
- receptor protein
- intracellular signaling proteins
- effector proteins
3 effector proteins
- metabolic enzyme
- transcription regulatory protein
- cytoskeletal protein
Effector protein that altered cell shape or movement
cytoskeletal protein
Effector protein that altered gene expression
transcription regulatory protein
Effector protein that altered metabolism
metabolic enzyme
cells produce signals that they
themselves respond to
autocrine signalling
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.
synaptic signalling
depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body
endocrine signalling
depends on local mediators that are
released into the extracellular space and
act on neighboring cells.
paracrine signalling
2 mechanisms of receptors
cell-surface receptors
intracellular receptors
communication between cells in multicellular organisms is mediated by
extracellular signal molecules
extracellular signal molecule
ligand
Reception of the signals depends on ___ at the cell surface, which bind the signal molecule
receptor proteins
they process the signal inside the
receiving cell and distributing it to the appropriate intracellular targets
intracellular signaling proteins
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.
effector proteins
he fundamental features of cell signaling have been conserved throughout the
evolution of the _____
eukaryotes
Expound the cell signaling in budding yeast
the response to mating factor depends on
* cell-surface receptor proteins
* intracellular GTP-binding proteins
* protein kinases
requires cells to be in direct membrane-membrane contact
Contact-dependent signaling
they are high specificity of binding site of receptors
target cells
Their extracellular domains may be released from the signaling cell’s surface by proteolytic cleavage and then act at a distance.
Transmembrane signal proteins
the target cell responds by means of a _____
receptor
binds the signal molecule and then initiates a response in the
target cell.
receptor
The binding site of the receptor has a complex structure that is shaped
to recognize the signal molecule with _____
high specificity
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
Some small signal molecules,
by contrast, diffuse across the plasma membrane and bind to receptor proteins inside the target cell
intracellular receptors
each cell is programmed to respond to ____ of extracellular signals
specific combinations
cell responds to the signals ____
selectively
if deprived of appropriate survival signals, a cell will undergo a form of cell suicide known as
apoptosis
a signal molecule often has __ __ on different types of target cell
different effects
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.
three major classes of cell-surface receptor proteins
ion-channel coupled receptors
g-protein coupled receptors
enzyme-coupled receptors
converting an extracellular
ligand-binding event into
intracellular signals that alter the
behaviour of the target cell
signal transducers
Ion-channel-coupled receptors, also known as __ or __
transmitter-gated ion channels or ionotropic receptors
involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells
ion-channel-coupled receptors
Ion-channel-coupled receptors is mediated by _______
neurotransmitters opening or closing an ion channel
what happens in ion-channel receptors?
- transmitter-gated ion
channels or ionotropic
receptors - electrically excitable cells
- neurotransmitters
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
mediates the interaction between the activated receptor and this target protein
trimeric GTP-binding protein (G protein)
how does G-proteins work?
can change the concentration of small intracellular signaling molecules OR change ion permeability
function as enzymes or associate directly with enzymes that they activate
enzyme-coupled receptors
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
intracellular signaling molecules are small chemicals, which are often
called _______
second messengers
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
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
phosphorylation enzymes
protein kinase - on
protein phosphatase - off
2 types of protein kinase
serine/threonine kinase
tyrosine kinases
A protein kinase covalently adds a phosphate from ATP to the signaling protein, and a protein phosphatase removes the phosphate.
phosphorylation
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
switches of GTP-binding proteins
GTP - on
GDP - off
2 types of GTP-binding proteins
trimeric GTP-binding proteins
monomeric GTP-binding
proteins
help relay signals from G-protein-coupled receptors that activate them
G-proteins
help relay signals from many classes of cell-surface receptors
small monomeric GTPases
drive the proteins into an “off” state by increasing the rate of hydrolysis of bound GTP
GTPase-activating proteins (GAPs)
activate GTP-binding proteins by promoting the release of bound GDP, which allows a new GTP to bind.
guanine nucleotide exchange factors (GEFs)
a sequence of two inhibitory steps can have the same effect as one activating step
double-negative activation
an activated intracellular signalling molecule should interact only with the appropriate __ __
downstream targets
2 characteristics of complementary surfaces
high affinity and specificity
The ability of downstream target proteins to simply ignore such signals respond only when the ___
upstream signal reaches a high concentration or activity
level
involves scaffold proteins
localization
holds the protein in close proximity;
interact at high local concentration;
sequentially activated rapidly
signaling complexes
phosphorylated cytoplasmic tail of the receptor serve as
Docking sites
which bring together groups of interacting signaling proteins into signaling complexes, often before a signal has been received
Localization (scaffold proteins)
they can interact at high local concentrations and be sequentially activated rapidly, efficiently, and selectively in response to an appropriate extracellular signal
Scaffold proteins
holds the protein in proximity; interact at high local concentration; sequentially activated rapidly
Signaling complexes
form only transiently in response; around a receptor
Signaling complexes
production of _____which recruit specific intracellular signaling proteins
Phosphoinositides
Specialized behaviors that produce appropriate for the cell function that system controls (7)
- Response timing
- Sensitivity to extracellular signals
- Dynamic range
- Persistence
- Signal processing
- Integration
- Coordination
Number or affinity; amplification
Sensitivity to extracellular signals
Responsiveness
Dynamic range
Transient response; prolonged or permanent
Persistence
Switchlike response; oscillatory response
Signal processing
Multiple inputs
Integration
Multiple responses
Coordination
speed of response depends on the nature of _____
intracellular signaling molecules
Signaling if only changes in proteins already present in the cell (altered protein function)
Occurs rapidly: allosteric change in a neurotransmitter-gated ion channel
changes in gene expression and the synthesis of new proteins (altered protein synthesis)
Occurs in minutes or hours, regardless of mode of signal delivery
response fades when a _____
signal ceases
2 types of abrupt responses when signal concentration rises beyond some threshold value
Sigmoidal
Discontinuous or all-or-none
low concentrations of stimulus do not have much effect, but then the response rises steeply and continuously at intermediate stimulus levels
Sigmoidal response
response switches on completely (and often irreversibly) when the signal reaches some threshold concentration
Discontinuous or all-or-none
Smoothly graded response
hyperbolic
the output of a process acts back to regulate that same process
feedback loops
output stimulates its own production
Positive feedback
output inhibits its own production
Negative feedback
- 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
steepen the response – sigmoidal or all-or-none response
Positive feedback
Self-sustaining, bistable, can have switches
Positive feedback
counteracts the effect of a stimulus
* limits the level of the response
Negative feedback
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
Delay in negative feedback
Oscillations
respond to changes in the concentration of an extracellular signal molecule
Adaptations
cells and organisms can detect the same percentage of change in a signal over a wide range of stimulus strengths
Adaptation or desensitization
Some ways that the cell may adapt
Receptor sequestration
Down-regulation
Inactivation
Inactivation of signaling protein
Production of inhibitory protein
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
What senses depend on G-proteins?
Sight, smell. Taste
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
it function is to couple the receptor to enzymes or ion channels in the membrane.
trimeric GTP-binding protein (G protein)
3 protein subunits of G proteins
a, B, and y
GTPase and becomes inactive when it hydrolyzes its bound GTP to GDP
GTPase Activating Proteins
When a subunit has GDP bound and the G protein is inactive
Unstimulated and inactivated
Activation of GPCR
acts like guanine nucleotide
exchange factor (GEF)
Cyclic AMP is synthesized from ATP by an enzyme called
Adenylyl cyclase
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
acts as a second messenger in some signaling pathways
Cyclic AMP
c-AMP is continuously destroyed by
cyclic AMP phosphodiesterases
stimulatory G protein activates adenylyl cyclase
Gs (stimulatory)
What regulate the production of cyclic AMP
G-proteins
What happens in pertussis toxin (whooping cough)
ADP ribosylation of the α subunit of Gi
What happens in cholera toxin?
ADP ribosylation that alters the Gs α subunit
Inhibitory of adenylyl cyclase
Gi (inhibitory)
cAMP exerts its effects mainly by activating what? _____
cyclic-AMP dependent protein kinase (PKA)
Adrenal cortex: Cortisol secretion
Adrenocorticotrophic hormone (ACTH)
Ovary: Progesterone secretion
Luteinizing hormone (LH)
Thyroid gland: thyroid hormone synthesis and secretion
Thyroid-stimulating hormone (TSH)
Muscle: Glycogen breakdown
Adrenaline
Bone resorption
Parathormone
A specific transcription regulator called ______ recognizes this sequence
CRE-binding (CREB) protein
Increase in heart rate and force of contraction
Adrenalin
cAMP activates the gene that encodes the hormone ____
Somatostatin
Glycogen breakdown in liver
glucagon
[PI(4,5) P2]
phosphatidylinositol 4,5-bisphosphate
Water absorption in kidney
Vasopressin
PKA inactive state:
two catalytic subunits and two regulatory subunits
PKA phosphorylates specific ___ and _____
Serines and threonines on target proteins
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)
The activated phospholipase then cleaves the PI(4,5)P2 to generate two products:
inositol 1,4,5-trisphosphate (IP3) and diacylglycerol
PKA activated state:
Released catalytic subunits
The regulatory region of the somatostatin gene contains a short cis-regulatory sequence
cyclic AMP response element (CRE)
CREB can transform a ___ cAMP signal into a ___-term change in a cell
Short, long
What does diacyglyerol activates?
activate protein kinase C (PKC)
Acts on inositol phospholipid signaling pathway
phospholipase C-β (PLCβ)
G protein called ___ activates GEF (___) that activates a monomeric GTPase (Rho family) which regulates the actin cytoskeleton
G12
guanine nucleotide exchange factor
Activates phospholipase C-B
Protein Gq
Cite the process of IP3 activation
endoplasmic reticulum IP3-gated Ca2+-release channels (IP3 receptors) increases concentration of Ca2+ in the cytosol
What are the specific GPCRs to recognize odors which acts through cAMP
Olfactory receptors
What senses depend on GPCRs that regulate ion channels?
Smell and vision
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
Example of G12 protein
Acetylcholine
They activate an olfactory-specific G protein (known as Golf), which in turn activates ______
adenylyl cyclase
How many olf receptors in human?
350
chemical signals detected in a different part of the nose that are used in communication between members of the same species
Pheromones
receptor activation stimulated by light causes ___ in the level of cyclic nucleotide
A fall
stack of discs; contains cyclic-GMP-gated cation channels
phototransduction apparatus
What is the crucial in vision? (clue: aside from cAMP)
Cyclic GMP
continuous rapid synthesis
Guanylyl cyclase
rapid degradation (by what enzyme?) controls the concentration of cyclic GMP in the cytosol
cyclic GMP phosphodiesterase
responsible for noncolor vision in dim light
Rod photoreceptors (rods)
responsible for color vision in bright light
cone photoreceptors (cones)
___ bound to these channels keeps the rhodopsin open in the dark
Cyclic GMP
In the light, it happens due to decreases the cyclic GMP conc. and closes the cation channel
Hyperpolarization
It phosphorylates the cytosolic tail of activated rhodopsin on multiple serines
rhodopsin kinase (RK)
activated by a photon of light
Rhodopsin
The isomerization of all-trans retinal alters PROCESS
conformation of transducin (Gt) → activate the cyclic GMP phosphodiesterase →hydrolyzes cyclic GMP → GMP levels fall
This hormone relaxes smooth muscles in the walls of blood vessels
Nitric oxide (NO)
Inhibits rhodopsin kinase (RK)
Arrestin
What stimulates NO synthesis?
acetylcholine
diffuses out of the cell into neighboring smooth muscle cells
Nitric Oxide (NO)
GPCRs 3 modes of adaptation
- receptor sequestration
- receptor down-regulation
- receptor inactivation
- prevents the activated receptor from interacting with G proteins * adaptor protein
Arrestin desensitization
