BS161.cell communication1&2
ras
- G protein -binds to GDP or GTP-g protein that is working with receptor kinases -activated when it binds to an adaptor protein and changes shape -activated Ras releases GDP, and binds GTP
NONPOLAR: (soluble, cytosolic, intracellular receptor) cross using _____________. - non-covalent interactions -receptor changes shape, then the receptor can:
cross into nucleus and bind to DNA and proteins
signaling molecules
carries information from one cell to the next
what does termination do
cellular response is stopped- termination protects the cell from overreacting to existing signals which helps the cell have an appropriate level of response. it allows the cell to respond to new signals
how does phosphorylation affect proteins?
-ATP is dephosphorylated -"target" protein is phosphorylated -phosphorylated protein can interact with other molecules -phosphorylation can also cause a protein to: change function and location in the cell
what can MAPKKK bind to
-Ras -bind specifically to the inactive MAPKK and ATP
what happens after Ras is activated
-active Ras binds inactive MAPKKK -when they interact, MAPKKK changes shape so now MAPKKK is active
what are two steps of the fight or flight response where the signal is amplified
-adenylyl cyclase producing cAMP -protein kinase A phosphorylates protein targets
what. happens when adenylyl cyclase is activated?
-an enzyme -when this enzyme gets activated (binds to a g protein), it catalyzes a chemical reaction that is the production of cyclic AMP from ATP -part of a cyclic ring that is formed with the other carbon atoms that are part of that sugar
polar
-cell-surface -not able to cross the cell membrane by simple diffusion -weak intermolecular forces
what happens when a ligand gated channel is activated?
-channel opens and ligand binds -allows ions to diffuse from an area of high concentration to low concentration (facilitated diffusion) allows ion concentration to increase until equilibrium is reached -channel closes when ligand releases from the channel
if specific receptors are present, binding of a signaling molecule leads to_______. if they are not, the cell is ___________________.
-downstream effects -not able to respond
all receptors:
-interact with a specific ligand -change shape after binding the ligand
non-polar
-intracellular -able to cross the cell membrane by simple diffusion -weak intermolecular forces
how G proteins are activated
-ligand binds to receptor (quick and not permanent) -receptor changes shape which allows it to interact w G protein -G protein is still inactive bc it is binding to GDP -has to exchange GDP in for GTP -GDP is going to leave the G protein and GTP is going to bind and exchange -G protein is bound to GTP and now active -GTP and GDP shape are different
what would happen if it were harder to remove GDP from Ras
1. Ras would not be activated as frequently 2. cell division would decrease
how is signal transduction controlled/terminated?
-ligand diffuses away from receptor goes back to its original shape -g protein: hydrolyzes GTP (removes phosphate) which inactivates G protein -enzymes degrade cAMP to become AMP which terminates the process -phosphatases removes phosphates so anything activated by phosphate is now back to inactive form
what can an active MAP kinase kinase do?
-phosphorylate something
what is the final result in Ras/MAPK pathway
-phosphorylated MAPKK changes shape and is now activated
what series of events happens after a G protein coupled receptro binds to a ligand?
-the G protein is binding to GTP now -this happened after the receptor changes shape -the change in shape allowed the receptor to interact with the G protein
How G proteins are inactivated
-the G proteins inactivates itself by hydrolyzing the GTP -hydrolysis of GTP: the G protein is going to remove one of the phosphates -now it is bound to GDP meaning it is inactive
what happens when a receptor kinase is activated?
-when ligand brings proteins together, they become associated through IMF's and form a dimer -when binds to a ligand, they change shape enough for receptor to bind to ATP -receptor has kinase activity and transfers phosphate from ATP to another part of receptor -phosphorylation adds negative charge to receptor and changes shape which allows it to interact w other proteins in cytosol -receptor binds signal transduction proteins:cannot interact w inactive receptor but can interact w phosphorylated receptor
Some cells undergo the cell cycle and mitosis but do not undergo cytokinesis. If a cell starts with 10 picograms (pg) of DNA and completes the cell cycle without undergoing cytokinesis, how much DNA will be found in the cell?
20 pg
Testoterone is an example of a steroid hormone that binds to an intracellular receptor. Some individuals are genetically male (XY), and produce testosterone, but have female external characteristics. Which of the following is likely a cause?
A mutation prevents the receptor from binding to the testosterone ligand
what is the role of ATP in allowing the protein to bind to the square molecule?
ATP donates a phosphate to the protein, changing its shape so it can fit the square molecule
how does phosphorylation inactivate a protein?
ATP donates a phosphate to the protein, changing its shape so it can no longer fit the square molecule
The image shows the activation of a G protein-coupled receptor pathway. Which of the following describes a possible amplification step in this pathway?
Active protein kinase A phosphorylates many different protein targets
POLAR: after ligand interacts with the receptor, the receptor __________. then the receptor can ___________________.
changes shape; interact with molecules in cytosol
What will happen to cell division if the signaling molecule (ligand) is absent, but the Ras protein is always bound to GTP and why
Cell division would increase because Ras-GTP is the active form of the signal transduction protein for cell division.
Two different types of cells from the same organism were exposed to a ligand. Cell type 1 shows a cellular response, but cell type 2 does not. Which best explains the mechanism for this difference?
Cell type 2 does not have a receptor for this ligand.
ligands
communications between cells
Compared to the cell in G1, the number of chromosomes in one cell _______ after the S phase and _______ after the M phase.
Does not change; does not change
change shape
constructing/deconstructing cytoskeleton
how is a G protein activated?
GDP is removed from the G protein and is replaced by GTP
G protein is binding
GDP or GTP
although the structures of G proteins vary, all G proteins are bound to:
GDP or GTP
What is the general role of GTP binding in signal transduction?
GTP changes the shape of G proteins, allowing new interactions to occur
What happens after a signaling molecule binds to its receptor and flips a molecular switch?
Following receptor activation, signaling pathways transmit the signal to targets in the interior of the cell, the cell responds, and eventually the signal is terminated. In the next two sections, we examine the signaling pathways activated by G protein-coupled receptors and receptor kinases.
what is deactivated when bound GTP is hydrolyzed to GDP + Pi?
G proteins
If a protein is activated by phosphorylation, the actions of which enzyme will inactivate the protein?
phosphatase
Where in the G protein-coupled receptor pathway does a phosphatase act in signal termination
On the protein target
how does Ras participate in signal transduction?
Ras binds to and activated the MAP kinase kinase kinase
what does active Ras do
Ras binds to and activates MAP Kinase Kinase Kinase using protein:protein interactions
What is the order of events in cell communication?
Receptor activation; Signal transduction; Response; Termination
All cell signaling pathways between cells involve:
Receptors that change shape after ligand binding
Fill in the blanks to complete the statement: in cell communication, receptors bind to _________ ligands using ________.
Specific; noncovalent interactions
correctly describes the activation of the G protein?
The activated receptor changes shape and activates the G protein.
After a steroid hormone binds to its intracellular receptor, transcription of specific genes occurs. How does this happen?
The activated receptor moves into the nucleus and binds to DNA.
The molecule caffeine, structure shown below, binds to the adenosine receptor. Based on your knowledge of functional groups and amino acid structures, how might caffeine and the receptor interact?
The carbonyl group of caffeine could form a hydrogen bond with a serine in the receptor.
What could happen if a cell does not terminate signal transduction?
The cell would not respond appropriately to new signals
Which of the following would occur if a ligand binds to a G protein coupled receptor and the receptor is activated?
The concentration of G proteins bound to GDP would decrease
If a spindle fiber fails to attach to one sister chromatid during M phase and the cell continue through mitosis, what will be true about the genetic information in the daughter cells and why will this be true?
The genetic information will not be identical because the affected sister chromatids will not separate during anaphase.
A cell has a mutation that results in higher levels of phosphorylated proteins than normal cells without the mutation. What kind of mutation occurred and what reasoning leads to this claim?
The mutation created a nonfunctional phosphatase protein, since phosphatases normally remove phosphates from proteins.
What impact does a phosphatase have on a signal transduction protein?
The phosphatase removes a phosphate causing the protein to change shape.
When a steroid hormone binds to an intracellular receptor, what happens after the receptor changes shape?
The receptor activates transcription.
what happens to a ligand-gated ion channel receptor when it is activated?
The receptor changes shape and opens a channel so ions can cross the membrane.
Signal transduction refers to:
The sequential activation of proteins inside the cell to generate a cellular response.
what determines whether a cell responds to a signaling molecule?
a cell responds to a signal only if it has receptors that are able to bind to the signaling molecule
g-protein coupled receptor
a cell-surface receptor -when a ligand binds to a G protein-coupled receptor, the receptor couples to, or associates with a G-protein
what is a g-protein
a complex protein that is associated with the membrane -not transmembrane but linked to the membrane
receptor kinases
a kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a substrate - to catalyze this reaction, it binds both ATP and the substrate in phosphorylation
what does active MAPKKK transfer
a phosphate from ATP to MAPKK
what does a signaling molecule bind to and what does it do
a receptor protein on or in the responding cell and the responding cell changes its activity or behavior
a cell that responds to the same signal but responds differently could have:
a receptor that binds to the same ligand but has different signal transduction proteins
what is a g-protein coupled receptor
a receptor that is able to interact with a G-protein
What is typically part of the termination of G-protein coupled receptor pathway? (hint: see figure 9.13)
cAMP is converted to AMP
phosphorylated receptor: -activated -terminated
activates by kinase adding a phosphate terminates by phosphatase removing phosphate
g protein -activates -terminates
activates: GDP is released and GTP is added terminates: phosphate is removed from GTP, producing GDP
second messenger binding to a protein -activates -terminates
activates: production of second messenger terminates: destruction of second messenger
protein: protein synthesis -activates -terminates
activates: the binding of a protein to another protein -terminates: the protein unbinds from the other protein
changing metabolism
activating/inactivating eznymes
how is phosphorylation regulated?
active kinases add phosphates to other proteins active phosphatases remove phosphates from other proteins
why is phosphorylation important
because it alters the activity of the substrate: when a protein is phosphorylated by a kinase, it typically becomes active and is switched on
why does a cell-surface receptor rely on signal transduction?
because the receptor uses up all its energy when it changes shape
where does cell communication in complex multicellular eukaryotes?
between cells within the same organism
where does cell communication occur in prokaryotes and eukaryotes?
between individual organisms
what do all kinases do?
bind to ATP and something else and transfer phosphate from ATP to other molecule
receptor kinases that ras-MAP kinase pathway is associated with:
bind to ligands that are involved with cell division or cell growth-growth factors
some proteins change shape when they ____________
bind to other molecules
how does the signal usually activate the receptor and what happens as a result
by causing a conformational change in the receptor. As a result, some receptors bind to and activate other proteins located inside the cell
describe two differences between active and inactive forms of a G protein
difference 1: the G protein is bound to GTP instead of GDP difference 2: the G protein shape is different (allows it to interact with other proteins and carry out different functions)
active receptor is
dimer and phosphorylated
"eat"
endocytosis
what are G proteincoupled receptors
evolutionary conserved and all have similar molecular structure
secrete more signals
exocytosis
what happens when a signaling molecule binds to a receptor on a responding cell?
first step-receptor activation
Ras is a:
g protein
Generally speaking, if cells have normal kinases but a mutant, nonfunctional form of a phosphatase, we would expect the mutant cells to have _________ levels of ___________ compared to wildtype cells without the mutations
higher, phosphates
before interacting with a kinase, the serine side chain contains a hydroxyl group, which can form _____________
hydrogen bon interactions
autocrine signaling
important to multicellular organisms during the development of the embryo-sometimes used to maintain developmental decision- can be used by cancer cells to promote cell division
changes in shape allow proteins to __________________-
interact with other molecules
one receptor:
interacts with many signaling proteins bc at first step we have amplification of the signal
What is NOT a type of receptor found on the cell's plasma membrane?
intracellular receptor
when a receptor kinase is activated, cytoplasmic proteins bind to the phosphate groups on the active receptor. Based on the structure of phosphate, what type of interaction likely occurs between the cytoplasmic proteins and the receptor?
ionic
AFTER the serine is phosphorylated, the serine can form _____________ within the protein and other molecules
ionic bond interactions
a cell does NOT respond to the ligand because
it does not have a receptor to bind to the ligand, so the signal transduction is not activated and there is no cellular response
Which enzyme transfers a phosphate from ATP to a protein?
kinase
which enzymes adds phosphates to proteins?
kinase
die
lead to specific changes in the DNA
cells-words
ligands
the three types of cell surface receptors are ________________, and can create a cellular response in the _____________.
ligands-gated ion channels, G-protein-coupled receptors, and receptor kinases; cytoplasm and the nucleus
ligand
means to bind signaling molecule
inactive receptor is
monomer and dephosphorylated
how do GDP and GTP bind to G proteins
non-covalently
receptors for ______ ligands are typically in the interior of the cell
nonpolar
phosphatase and kinase important
not all phosphatases terminate a signal and not all kinases activate a signal
what happens during signal transduction
one molecule activated the next molecule, which activates the next and so on
active MAPKK transfers:
phosphate from ATP to MAPK
one kinase:
phosphorylates many proteins
when kinase is activated what can it do?
phosphorylates other proteins
what can active MAPK do in nucleus
phosphorylates proteins specifically inside the nucleus -using phosphates from ATP
receptors for _____ ligands are typically on the cell surface
polar
In cell communication, cell-surface receptors typically bind signaling molecules; intracellular receptors bind signaling molecules
polar; non-polar
one adenylyl cyclase:
produces many cAMP -can activate many targets of cyclic AMP
cells-ears
receptors
phosphatases
remove a phosphate group through dephosphorylation
divide
replicate DNA
cyclic AMP
second messenger signaling -first messenger is the ligand -cyclic AMP relays the "signal" to other proteins inside the cell -when adenylyl cyclase is activated, cyclic AMP levels are increasing in a cell
receptor activation
signal binds to the receptor and the receptor is turned on, or activated
During which step of cell signaling does amplification typically occur?
signal transduction
what advantages arise from having signal transduction that relies on many different proteins?
signal transduction cascades require many proteins, which allows cells to: 1. produce different responses from the same receptor and ligand 2. fine-tune the response by adjusting the activity of different proteins in the signal transduction process 3. amplify the signal to generate a robust response
paracrine signaling
signaling between two cells that are close to each other. signaling can move by diffusion between the two cells
endocrine signaling
signaling by means of molecules that travel through bloodstream
A transmembrane protein on the surface of one cell acts as the __________________, and a transmembrane protein on the surface of an adjacent cell acts as the _____________.
signaling molecule; receptor
growth factor
small water-soluble molecule in paracrine signaling-type of signaling that causes the responding cell to grow, divide, or differentiate
many signaling molecules such as growth factors are ______, ______ proteins that cannot pass through the hydrophobic core of the plasma membrane
small, polar
change gene expression
start/stop trasncription
what is the last step after cellular response
termination
how is an active G protein inactivated?
the G protein hydrolyzes GTP to remove a phosphate and GDP is produced
what would happen if the GTP were not hydrolyzed?
the G protein would be active longer
what would be the effect of nonfunctional phophatase?
the amount of phosphorylated proteins would increase, since phosphatases remove phosphates from proteins
when a signaling molecule binds to a receptor, what determines the specific response of the cell?
the cells response depends on the set of proteins that is found in the cell, as different cell types have different sets of intracellular proteins and signaling pathways
active MAPK is transported into...
the nucleus
what happens after receptor activation
the receptor triggers a series of downstream events in a process called signal transduction
two cells can respond to the ligand in different ways becuase
the receptors have the same ligand-binding region but interact with different signal transduction proteins, which leads to different cellular responses
how and why does the protein change as a result of phosphorylation?
the shape changed because new interactions can now occur within the protein
what is an important aspect of signal transduction
the signal is often amplified at each step in the pathway which as a result, a low signal concentration can have a large effect on the responding cell
ligand binding site
the signaling molecule binds to a specific part of the receptor protein -the bond formed is noncovalent and highly specific
what happens after signal transduction
there is cellular response which can take different forms depending on the nature of the signal and the type of responding cell
proteins return to their original shape when they ________________
unbind/dissociate
explain how a kinase enzyme can participate in signal amplification
when a kinase is activated, it can phosphorylate many proteins because it is an enzyme, meaning that it can catalyze a reaction many times without being used up. Because one kinase can act on many proteins, the signal is amplified
what does the location of a particular receptor in a cell depend on
whether the signaling molecule is polar or nonpolar
can the response be terminated at any point along the signaling pathway?
yes
can the same signaling molecule have different effects in different types of cells?
yes