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Define Signal Transduction Pathway
Vocab 7.1 Cells Detect a Variety of Signals
A sequence of molecular events and chemical reactions whereby a stimulus/signal is translated into a response of the cell.
Examples of a stimulus include: hormones or a neurotransmitter binding to a receptor.
What are the 3 components of a signal transduction pathway?
Concept 7.1 Cells Detect a Variety of Signals
Signal
Receptor (a protein)
Response
What are the 4 types of signals?
Concept 7.1 Cells Detect a Variety of Signals
Autocrine signals
Juxtacrine signals
Paracrine signals
Hormones
Define Autocrine Signals
Vocab 7.1 Cells Detect a Variety of Signals
A chemical signal that binds to and affects the cell that made it.
Define Juxtacrine Signals
Vocab 7.1 Cells Detect a Variety of Signals
A chemical signal that binds to and affects only adjacent cells and cells that are in direct contact with the cell producing the signal.
Define Paracrine Signals
Vocab 7.1 Cells Detect a Variety of Signals
A chemical signal that binds to and affects nearby cells.
Define Hormone Signals
Vocab 7.1 Cells Detect a Variety of Signals
A chemical signal that travels via the circulatory system (in animals) or the vascular system (in plants) to bind to and affect distant cells.
What are the 3 components of a signal transduction pathway?
Concept 7.1 Cells Detect a Variety of Signals
Signal
Receptor (a protein)
Response
For a cell to respond to a signal, it must have what?
Concept 7.1 Cells Detect a Variety of Signals
A specific receptor.
Where does signal-receptor interaction mostly occur?
Concept 7.1 Cells Detect a Variety of Signals
At the cell membrane.
Typically, what do the events of signal transduction do to the signal’s effect?
Concept 7.1 Cells Detect a Variety of Signals
They amplify/strengthen the effect.
Responses to a signal may involve what to bring about a response?
Concept 7.1 Cells Detect a Variety of Signals
Enzymes and transcription factors that are activated or inactivated.
Define Crosstalk-Interactions
Vocab 7.1 Cells Detect a Variety of Signals
Interactions between different signal transduction pathways.
Pathways are not able to branch off, true or false?
(If false, correct the statement.)
Concept 7.1 Cells Detect a Variety of Signals
False, pathways are able to branch off. So, one activated protein is capable of activating multiple pathways.
Is it possible for multiple transduction pathways to converge/meet/intersect?
Concept 7.1 Cells Detect a Variety of Signals
Yes
When multiple pathways are connected, is it possible for one pathway to be activated while another is inhibited?
Concept 7.1 Cells Detect a Variety of Signals
Yes, this is possible!
Which is an example that explains how a juxtacrine signal functions in the human body?
a. At the junction of two nerve cells, one of the cells secretes a neurotransmitter molecule that diffuses over to the neighboring cell, where it binds and stimulates an electrochemical response.
b. To signal hunger, cells in the stomach secrete a peptide that circulates through the blood and binds to receptors on cells in the hypothalamus in the brain.
c. A cell in a developing embryo has a cell surface protein that directly contacts a receptor on a neighboring cell, causing it to change its gene expression pattern.
Question 7.1 Cells Detect a Variety of Signals
c. A cell in a developing embryo has a cell surface protein that directly contacts a receptor on a neighboring cell, causing it to change its gene expression pattern.
(Option A is an example of a paracrine signal, and option B is an example of a hormonal signal.)
A biologist identifies a new signal transduction pathway in mouse cells that are stimulated by the compound L-alanine. Which statement makes a reasonable prediction about how D-alanine will interact with this pathway, and why?
a. D-alanine will likely bind to the receptor and stimulate the signal transduction pathway because it has the same chemical formula as L-alanine.
b. D-alanine will likely not bind to the receptor because it does not have the correct orientation of functional groups to match up with the receptor site.
Question 7.1 Cells Detect a Variety of Signals
b. D-alanine will likely not bind to the receptor because it does not have the correct orientation of functional groups to match up with the receptor site.
(It’s important to note that binding is very specific.)
The human pituitary gland secretes thyroid-stimulating hormone (TSH). TSH stimulates the thyroid gland to release thyroxine, a hormone that regulates metabolism. TSH does not affect heart cells. What can be concluded from this?
a. Thyroid cells, but not heart cells, contain the gene encoding the protein that makes up the TSH receptor.
b. Both thyroid and heart cells make TSH receptors on their surfaces, but only thyroid cells respond to TSH.
c. Both thyroid and heart cells have the gene for the TSH receptor, but only thyroid cells express the gene.
c. Both thyroid and heart cells have the gene for the TSH receptor, but only thyroid cells express the gene.
(Every cell contains the same DNA, however, the thyroid cells in this case expressed the genes for the receptor. Not all cells make receptors for every signal.)
What is important about receptor proteins?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
They have very specific binding sites for chemical signal molecules.
What is the term used for chemical signal molecules?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Ligands
Define Ligands
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
A specific chemical signal molecule that binds to and fits in a protein receptor site.
What happens to a receptor once a ligand binds to it?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
The ligand causes the receptor protein to change shape.
What happens to a ligand when the binding is reversed?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
It becomes altered.
Receptor (R) — Ligand (L) binding is shown by what equation
Receptor (R) — Ligand (L) dissociation is shown by what equation?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
R + L -K₁-> RL (Binding)
RL -K₂-> R + L (Dissociation)
Binding and dissociation each have a rate constant (k).
What is the equation for the rate of binding?
What is the equation for the rate of dissociation?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
k₁[R][L] (Rate of Binding)
k₂[RL] (Rate of Dissociation)
At equilibrium, the rate of binding equals the rate of dissociation. This is show by what equation?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Kɒ = k₂ / k₁ = [R][L] / [RL]
What is Kɒ?
Kɒ = k₂ / k₁ = [R][L] / [RL]
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Kɒ is the dissociation constant, a measure of the affinity of the receptor for its ligand.
Is it possible for the Receptor — Ligand binding to continue indefinitely/infinitely?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
No, eventually the cell will keep growing, which isn’t good, and typically would stop after the function is complete.
What happens as Kɒ decreases?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
As Kɒ decreases, the affinity increases.
What happens if receptors have very low Kɒ values?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
If receptors have low Kɒ then they can bind at very low ligand concentrations.
Which equation describes the rate of release of a ligand from a receptor? In all equations shown, “R” represents a receptor with no ligand bound, “L” represents a free ligand in solution, and “RL” represents a receptor bound to a ligand.
a. RL — k₁ —> R + L
b. R + L — k₂ —> RL
c. R — k₂ —> RL + L
d. R + L — k₁ —> RL
e. RL — k₂ —> R + L
Question 7.2 Receptors Bind Signals to Initiate a Cellular Response
e. RL — k₂ —> R + L
What are other chemicals that resemble ligands that can bind to receptors?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Agonist
Antagonists (inhibitors)
Define Agonist
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
A chemical substance that elicits a specific response in a cell or tissue. Has the same effect as a ligand.
Define Antagonist
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
A chemical inhibitor substance that binds to the receptor preventing the real ligand from binding and doesn’t set off signal transduction.
Caffeine is similar to adenosine and binds to the same receptors. Adenosine initiates signaling in nerve cells which reduces an individuals brain activity and wakefulness. Caffeine, however, ties up the adenosine receptors, allowing continued nerve cell activity. What is caffeine?
a. An agonist
b. An antagonist
Question 7.2 Receptors Bind Signals to Initiate a Cellular Response
b. An antagonist
What are the two types of receptors?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Membrane Receptors (In membrane)
Intracellular Receptors (Inside cell)
What binds to membrane receptors?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Large or polar ligands that can’t cross the lipid bilayer.
(Ex. Insulin)
What binds to intracellular receptors?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Small or nonpolar ligands that can diffuse across the cell membrane.
(Ex. Estrogen)
What are the 3 types of cell membrane receptors found in complex eukaryotes?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Ion Channels
Protein Kinase Receptors
G Protein-Coupled Receptors
Define Ion Channels
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
An integral membrane receptor protein that allows ions (ex. Na⁺, K⁺, Ca²⁺, Cl⁻) to diffuse across the membrane in which it is embedded.
(Note: Ion channels can be gated and non-gated. In this case, we are focusing on gated ion channels.)
What happens when a signal binds to a gated ion channel?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
Signal binding results in a change in shape of the channel protein, and the channel opens.
(Ex. The acetylcholine receptor on muscle cells is a ligand-gated ion channel.)
Define Protein Kinases
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
An enzyme that catalyzes phosphorylation, the addition of a phosphate group from ATP, of themselves and/or other proteins which changes their shape and functions.
(Note: Kinase means phosphorylation.)
(Ex. Insulin receptors phosphorylate itself and other insulin response substrates, resulting in glucose transporters added to the cell membrane.)
Define G Protein-Coupled Receptors
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
A class of receptors that change configuration upon ligand binding such that a G protein binding site is exposed on the receptor's cytoplasmic domain, initiating a signal transduction pathway.
What happens when a signal binds to a G Protein-Coupled Receptor?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
A G protein is activated which then activates an effector protein.
Define G Protein
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
A membrane protein involved in signal transduction; characterized by binding GDP or GTP.
What are the three polypeptide subunits of G proteins?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
The receptor
GDP and GTP (guanosine diphosphate & triphosphate)
An effector protein
What happens when a G protein binds to an activated receptor protein?
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
GDP (guanosine diphosphate) is exchanged for GTP (guanosine triphosphate).
And the ligand/signal, which is on the extracellular side, is typically released at the same time.
Define Effector Protein
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
In cell signaling, a protein responsible for the cellular response to a signal transduction pathway.
Define Intracellular Receptors
Vocab 7.2 Receptors Bind Signals to Initiate a Cellular Response
A receptor that binds its ligand inside the cell and responds to signals such as light or chemicals that can cross the cell.
Most intracellular receptors are transcription factors, true or false?
(If false, correct the statement.)
Concept 7.2 Receptors Bind Signals to Initiate a Cellular Response
True, after the binding of ligands, they move to the nucleus, bind to DNA, and alter gene expression.
(Ex. Cortisol receptors.)
Listed are dissociation constants for ligands and inhibitors of five different membrane receptors. In which case is the receptor’s affinity for an inhibitor much greater than the receptor’s affinity for its ligand?
a. L
b. M
c. N
d. O
e. P
Question 7.2 Receptors Bind Signals to Initiate a Cellular Response
c. N
When mammalian kidney cells were grown in culture and treated with a proteolytic enzyme (an enzyme that breaks down proteins), they lost the ability to respond to the hormone vasopressin but not to the hormone aldosterone. Which is a reasonable explanation for this?
a. The vasopressin receptor is embedded in the cell membrane with an external portion that binds its ligand, whereas the aldosterone receptor is an intracellular receptor.
b. Vasopressin requires a receptor to stimulate a signal transduction pathway, whereas aldosterone can stimulate a signal transduction pathway without binding to a receptor.
Question 7.2 Receptors Bind Signals to Initiate a Cellular Response
a. The vasopressin receptor is embedded in the cell membrane with an external portion that binds its ligand, whereas the aldosterone receptor is an intracellular receptor.
What are signals that work at long range known as? What is the mode of travel of these signals?
7.1 & 7.2 Review
Hormones which travel via the circulatory system (in animals) or the vascular system (in plants)
How does a ligand that is on the outside a cell result in a signal on the inside of the cell?
7.1 & 7.2 Review
It binds to a receptor and causes some changes in shape and function.
Kɒ and receptor-ligand affinity are ______ proportional/related.
7.1 & 7.2 Review
Inversely
Refer to the table. Compound X is the natural ligand that binds to a receptor and stimulates a signal transduction pathway associated with the receptor. Based on the info given in the table, what are the roles of compounds A, B, and C?
7.1 & 7.2 Review
A is an agonist
B is an antagonist
C has no role in this pathway
What are G proteins?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
A membrane protein involved in signal transduction; characterized by binding GDP or GTP.
What is RAS?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
RAS is a G protein that regulates cell division.
What happens if there is an abnormal activation of the protein RAS?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
RAS would be permanently bound to the GTP causing continuous cell division which can be found in some tumors.
Define Protein Kinase Cascade
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
A series of reactions in response to a molecular signal, in which a series of protein kinases activate one another in sequence, amplifying the signal at each step.
Define Mitogens
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
The ligands that stimulate cell division or mitosis.
What does the abbreviation MAPK stand for? (Hint: Related to RAS and Mitogens)
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
MAPK stands for Mitogen Activated Protein Kinase
Define Second Messengers
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Small molecules that diffuse through the cytosol to mediate some steps in a cascade. They amplify and distribute the signal.
(Ex. cyclic AMP (cAMP), Ca²⁺, and NO)
What can occur after the binding of a signal molecule to a receptor?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Once a signal molecule binds to a receptor, ATP & cAMP can be produced. cAMP (cyclic AMP) is a secondary messenger.
What does cAMP do?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
cAMP activates many enzyme targets.
Second messengers are often involved in _______ between different signaling pathways.
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Second messengers are often involved in crosstalks between different signaling pathways.
What are second messengers formed from?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Membrane phospholipids like PIP₂ which is located in the membrane.
Define Phosphatidyl inositol-bisphosphate (PIP₂)
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
A phospholipid in the cell membrane that is involved in cell signaling after a ligand binds to a nearby receptor.
The hydrolysis of PIP₂ results in two second messengers: _______ and ______.
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Inositol Triphosphate (IP₃) and Diacylglycerol (DAG)
Define Inositol Triphosphate (IP₃)
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
An intracellular second messenger derived from membrane phospholipids (specifically PIP₂).
Define Diacylglycerol (DAG)
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
In hormone action, the second messenger is produced by hydrolytic removal of the head group of certain phospholipids.
PIP₂ is a phospholipid which has a hydrophobic portion embedded in the cell mebrane: two fatty acid tails attached to a glycerol, which together forms ______.
The hydrophobic portion of PIP₂ is ______.
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
PIP₂ is a phospholipid which has a hydrophobic portion embedded in the cell mebrane: two fatty acid tails attached to a glycerol, which together forms Diacylglycerol (DAG).
The hydrophobic portion of PIP₂ is Inositol Triphosphate (IP₃).
What do Inositol Triphosphate (IP₃) and Diacylglycerol (DAG) do?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Inositol Triphosphate (IP₃) and Diacylglycerol (DAG) activate protein kinase C (PKC).
Define Protein Kinase C (PKC)
Vocab 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
A family of protein kinases that can phosphorylate many proteins, leading to a variety of cell responses.
_______ can be second messengers.
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Ca²⁺ ions can be second messengers.
Ca²⁺ ions are typically scarce inside cells. Ca²⁺ ion concentrations outside the cell and within the endoplasmic reticular (ER) are usually much higher. How is ion concentration maintained in the cell and ER membrane?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Ca²⁺ ions are pumped out of the cytoplasm keeping concentrations low.
What opens Ca²⁺ channels causing Ca²⁺ concentrations to increase rapidly?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Inositol Triphosphate (IP₃) & other signals
Entry of a sperm into an egg cell
What does Ca²⁺ ions do to protein kinase C?
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Ca²⁺ ions activate protein kinase C (PKC)
______ is a second messenger between ______ (a neurotransmitter) and the relaxation of ______ in blood vessels, allowing more blood flow.
Concept 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
Nitric oxide (NO) is a second messenger between acetylcholine (a neurotransmitter) and the relaxation of smooth muscle in blood vessels, allowing more blood flow.
A protein kinase cascade can amplify an intracellular signal by:
a. opening gap junctions to allow diffusion of signals from neighboring cells.
b. using nitric oxide to quickly diffuse into cells, amplifying the response.
c. activating one kinase molecule that can then trigger the activation of many proteins.
Question 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
c. activating one kinase molecule that can then trigger the activation of many proteins.
Biologists have found numerous genes in a single cell that encode cAMP-binding proteins. (cAMP is a known second messenger in signal transduction pathways.) Which statement makes a reasonable claim?
a. Only one of the cAMP-binding proteins could be a participant in a signal transduction pathway, while the others must have some other function in the cell.
b. All of the cAMP-binding proteins may be participants in different signal transduction pathways in a cell and are likely expressed at different times.
Question 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
b. All of the cAMP-binding proteins may be participants in different signal transduction pathways in a cell and are likely expressed at different times.
The drug sildenafil (Viagra) increases cGMP levels, so which enzyme is most likely inhibited by Viagra?
a. Phosphodiesterase
b. Protein kinase
c. Guanylyl cyclase
d. Protein phosphatase
Question 7.3 Signal Transduction Spreads the Response to a Signal through the Cell
a. Phosphodiesterase
What are the 3 ways that cells respond to signals?
Concept 7.4 Cells Change in Response to Signals in Several Ways
Differential gene expression
Opening ion channels
Changing enzyme activity
How do ion channels respond to signals?
Concept 7.4 Cells Change in response to Signals in Several Ways
Ion channels are signal receptors that respond by opening or closing.
What are two ways enzymes can be modified in signaling pathways?
Concept 7.4 Cells Change in response to Signals in Several Ways
Phosphorylation by a protein kinase changes enzyme shape (a covalent change).
cAMP binds noncovalently to an enzyme to change its shape.
What enzyme performs phosphorylation?
Concept 7.4 Cells Change in response to Signals in Several Ways
Kinase
What happens when enzymes are modified by phosphorylation and cAMP binding?
Concept 7.4 Cells Change in response to Signals in Several Ways
In both, an active site is exposed, and the enzyme catalyzes new reactions.
Which sequence lists the various mechanisms cells use to respond to signals in order, from shortest to longest response time?
a. Ion channel opening, enzyme activation/deactivation, differential gene expression
b. Enzyme activation/deactivation, differential gene expression, ion channel opening
c. Enzyme activation/deactivation, ion channel opening, differential gene expression
Question 7.4 Cells Change in Response to Signals in Several Ways
a. Ion channel opening, enzyme activation/deactivation, differential gene expression