Biology 353 Exam 3

1. Conformational change brings protein tyrosine kinases close together 2. Receptor dimerization 3. Autophosphorylation activates receptor tyrosine kinases 4. Hormone/ligand binds to extracellular subunits Which of the following correctly places the steps of the receptor tyrosine kinase in order? Possible Answers: 1,4,2,3 2,4,1,3 4,1,3,2 4,2,1,3

4,2,1,3 Explanation: The first step in all signaling pathways is ligand binding. This causes the extracellular domains to dimerize, inducing a conformational change in transmembrane segments. The cytoplasmic protein tyrosine kinase domains are then then brought close so they can cross-phosphorylate leading to receptor tyrosine kinase activation. Insulin signaling is a primary example of receptor tyrosine kinase signal transduction, and its receptor is already dimerized.

Glucagon and its liver receptor and epinephrine and its beta adrenergic receptor both activate __________ causing an increase in __________. Possible Answers: phospholipase C . . . protein kinase c the sodium-potassium pump . . . membrane potential adenylate cyclase . . . cAMP voltage gated Ca2+ channels . . . muscle contraction

Adenylate cyclase .... cAMP Explanation: These are examples of heterotrimeric G protein-dependent signaling. Glucagon and epinephrine hormones both cause GTP to bind to adenylate cyclase, which produces the second messenger cAMP.

Which of the following molecules is not considered to be a second messenger? Possible Answers: Calcium ion cAMP All of these are second messengers Diacylglycerol (DAG) Inositol 1,4,5 triphosphate (IP3)

All of these are second messengers Explanation: Second messengers are molecules that act within cells to either increase or decrease activity or amount of a final molecule. All of the answer choices are second messengers in various pathways.

Which of the following statements is true? Possible Answers: Transport proteins are identical in structure to gap junctions All transport proteins are asymmetric across the plasma membrane. All transport proteins are symmetric across the plasma membrane. All transport proteins are heterotetramers Some transport proteins are symmetric, while others are asymmetric across the plasma membrane.

All transport proteins are asymmetric across the plasma membrane. Explanation: Transport proteins (such as the GLUT1 transporter) are asymmetric. They have two conformational states that accept the ligand from the extracellular environment and release it inside the cell after transport

Which subunit of heterotrimeric G-proteins translocates downstream to activate its effector enzyme? Possible Answers: Beta subunit None of these answers All of these answers Gamma subunit Alpha subunit

Alpha subunit Explanation: When a G-protein is activated (in its ATP bound state), the alpha subunit dissociates from the beta and gamma subunits and binds to the effector enzyme for further activation and signal amplification downstream. For example, when adrenaline binds to the beta-andrenergic receptor, the alpha subnit dissociates from the beta+gamma subunits and activates adenylyl cyclase, which then produces cAMP, signaling for downstream protein targets to be phosphorylated.

Which of the following represents the state of the G protein when it is unactivated? Possible Answers: Beta and gamma units bound to GDP Beta and gamma units bound to GTP Alpha unit bound to GDP Alpha, beta, and gamma units bound to GTP Alpha, beta, and gamma units bound to GDP

Alpha, beta, and gamma units bound to GDP Explanation: In its unactivated state, a G protein is present as a heterotrimer consisting of an alpha, a beta, and a gamma subunit. This heterotrimer is bound to GDP. Upon activation by conversion of GDP to GTP, the G protein will dissociate into an alpha subunit separated from the beta and gamma unit (these two are still connected).

Which component of a neuron is responsible for electochemically stimulating nearby cells?

Axon Explanation: The axon ends in a terminal bud, which transmits signals to target cells by releasing neurotransmitters across the synapse. The soma is the body of the cell and contains the nucleus. This is where the majority of protein synthesis occurs. The dendrites receive electrochemical stimuli from other neurons and cells and transmit the signal to the soma and axon.

What is the function of the enzyme adenylate cyclase often seen in signal transduction pathways? Possible Answers: Conversion of ATP to ADP Conversion of GDP to GTP Conversion of ATP to cAMP Conversion of cAMP to ATP Conversion of GTP to GDP

Conversion of ATP to cAMP Explanation: Often following the activation of a G protein, ATP is converted to the second messenger, cAMP, by adenylate cyclase. This propagates the amplification of the signal transduction.

What is the function of phospholipase C? Possible Answers: Forms diacylglycerol (DAG) from inositol triphosphate (IP3) and phosphatidylinositol biphosphate (PIP2) Converts inositol triphosphate (IP3) into phosphatidylinositol biphosphate (PIP2) and diacylglycerol (DAG) Converts phosphatidylinositol biphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3) Forms phosphatidylinositol biphosphate (PIP2) from diacylglycerol (DAG) and inositol triphosphate (IP3) Converts diacylglycerol (DAG) into phosphatidylinositol biphosphate (PIP2) and inositol triphosphate (IP3)

Converts phosphatidylinositol biphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3) Explanation: The function of phospholipase C is to cleave phosphatidylinositol biphosphate (PIP2) into the two second messenger molecules, diacylglycerol (DAG) and inositol triphosphate (IP3). These can then act within signal transduction pathways to amplify ligand/receptor signals.

Phosphatidylinositol bisphosphate (PIP2) can be cleaved by phospholipase C to produce lipid-derived second messengers. Which of the following are the two second messengers derived from PIP2? Possible Answers: Diacylglycerol (DAG) and protein kinase A (PKA) Phosphatidylcholine and cyclic AMP (cAMP) Protein kinase C (PKC) and nitric oxide (NO) Inositol triphosphate (IP3) and protein kinase C (PKC) Diacylglycerol (DAG) and inositol trisphosphate (IP3)

Diacylglycerol (DAG) and inositol trisphosphate (IP3) Explanation: PIP2 gets cleaved into two smaller molecules by phospholipase C, and these two molecules are DAG and IP3. The protein kinases are not produced from this reaction, nor is cAMP or phosphatidylcholine. This is simply a matter of knowing that DAG and IP3 are the two most important lipid-derived second messengers.

How does cAMP regulate the action of Protein kinase A (PKA)? Possible Answers: Four molecules of cAMP bind to PKA and dissociate it into 2 catalytic subunits and 2 regulatory subunits cAMP phosphorylates PKA which sets it into action. cAMP does not affect the action of PKA Four molecules of cAMP bind only to the catalytic subunits of PKA which allows them to function cAMP is initially bound to PKA to prevent its action, and when it dissociates PKA is able to function

Four molecules of cAMP bind to PKA and dissociate it into 2 catalytic subunits and 2 regulatory subunits Explanation: The binding of four cAMP molecules to PKA dissociates it into two regulatory subunits and two catalytic subunits. The actual sites that the cAMP binds to, however, are allosteric sites - they are not directly on the regulatory sites or the catalytic sites.

A scientist is running an experiment to determine the effects of a new drug on cells. Aftering treating cells with the drug, the scientist observes an increase in the amount of diacylglycerol found within these cells. Based on this information, what type of receptor is this drug likely interacting with?

G coupled protein receptor

Which of the following is not a second messenger? Possible Answers: cAMP Calcium G-protein diacylglycerol cGMP

G-protein Explanation: There are many types of second messengers including diacylglycerol, cAMP, cGMP, calcium, and inositol trisphosphate. However, a G-protein is part of a pathway that utilizes second messengers, but is not one itself.

Which of the following statements about heterotrimeric G proteins and their receptors is incorrect? Possible Answers: A Cys-S linked palmitoyl group faces the extracellular region. G protein-coupled receptors may be desensitized by serine phosphorylation. G-protein coupled receptors contain nine transmembrane alpha helices. When GTP binds to the alpha subunit of the G protein, the beta-gamma subunit dissociates from the alpha subunit.

G-protein coupled receptors contain nine transmembrane alpha helices. Explanation: G protein-coupled receptors contain nine seven transmembrane alpha helices. All other statements are true of G protein-coupled receptors.

Which subclass of G-protein coupled receptors directly signal inhibition of adenylyl cyclase?

Gamma-alpha (inhibitory)

Which of the following is not a correct statement about G-proteins? Possible Answers: The α subunit of the G-protein detaches once GDP is converted to GTP The α subunit reattaches once the GTP gets hydrolyzed to GDP One mechanism of G-proteins activates the phosphoinositide cascade Gs, Gq, and Gi are 3 types of G-proteins Gs, Gq, and Gi are 3 types of G-proteins

Gs, Gq, and Gi are 3 types of G-proteins Explanation: Gs, Gq, and Gi are not types of G proteins. Instead, they are types of α subunits of a G-protein.

Which of the following is a possible consequence of activation of a G protein-coupled receptor? I. Increasing cAMP levels II. Increase the flow of sodium ions across the plasma membrane III. Increasing protein kinase C (PKC)

I and III Explanation: The G protein-coupled receptor (GPCR) is a signaling receptor found in many cells throughout the body. It utilizes a second messenger system to convey signals to the cell. This means that, upon activation, the GPCR will activate second messenger molecules such as cAMP that will cause biochemical changes inside the cell. One of the downstream molecules cAMP acts on is called protein kinase C (PKC). Recall that kinases are enzymes that facilitate the phosphorylation of molecules. PKC will phosphorylate several molecules that activate different signaling pathways. Note that ion transport (such as sodium ion transport) occurs when an ion channel is activated. G protein-coupled receptors are not ion channels; therefore, they do not facilitate the movement of ions across membranes.

How do diacylglycerol (DAG) and IP3 (inositol triphosphate) act as second messengers? I. Phospholipase catalyses the formation of DAG and IP3 from PIP2 (phosphatidylinositol-4,5-bisphosphate) II. IP3 increases intracellular calcium ion levels III. DAG stimulates protein kinase C IV. Protein kinase C activates protein kinases known as the MAP kinases Possible Answers: II and III I and II II, III, and IV I, II, III, and IV III and IV

I, II, III, and IV Explanation: Phospholipase C catalyses the formation of DAG (diacylglycerol) and IP3 (inositol triphosphate) from PIP2 (phosphatidylinositol-4,5-bisphosphate). IP3 promotes the influx of calcium ions into the cytoplasm while DAG stimulates protein kinase C.

What are some hormones that exert their actions by activating receptor tyrosine activity? I. Insulin II. Epidermal growth factor III. Platelet-derived growth factor IV. Epinephrine Possible Answers: I and II I and III I, II, and III II, III, and IV I, II, III, and IV

I, II, and III Explanation: Insulin, platelet-derived growth factor and, epidermal growth factor all use receptors that have intrinsic tyrosine activity. The hormones bind to the receptor which activates the tyrosine kinase. This in turn induces receptor transautophosphorylation and activation of SH2-domain downstream molecules. Epinephrine is a hormone that when bound, activates a G protein-coupled receptor and leads to activation of adenyl cyclase.

How does nitric oxide act as a second messenger? I. Nitric oxide activates guanylate cyclase. II. Nitric oxide promotes formation of the intracellular messenger cyclic guanosine monophosphate (cGMP). III. An increase of cGMP due to nitric oxide causes vasodilation. IV. Nitric oxide promotes formation of cyclic adenosine monophosphate (cAMP) Possible Answers: I and II II, III, and IV I and IV I, II, and III II and III

I, II, and III Explanation: Nitric oxide is a gas second messenger.It is also a neurotransmitter in the brain. Nitric oxide is produced by 3 enzymes: endothelial, induced, and neuronal nitric oxide synthases. Nitric oxide synthases require a calcium ions for the enzyme activity. Nitric oxide does act thru the cyclic guanosine monophosphate activation pathway.

Which of the following is not a direct function of cAMP? I. Amplification of signal II. Phosphorylation of molecules III. Activation of kinases Possible Answers: I only I and III II only I, II, and III

II only Explanation: cAMP is a second messenger molecule that activates several molecules. Second messenger molecules often amplify the original signal, allowing for the signal to travel all across the cell. One of the molecules activated by cAMP is protein kinase C (PKC). This molecule, as the name implies, is a kinase; therefore, it phosphorylates other molecules. Note that this is a function of protein kinase C, not a direct function of cAMP.

Signal transduction cascades are a very important component of communication between cells. A variety of different receptor types function by way of signal transduction, such as G protein-coupled receptors (GPCRs). After a signal transduction cascade has been initiated via a GPCR, which of the following is not a way in which the signal can be turned off? Possible Answers: Inactivation of the receptor by phosphatase enzymes Receptor activity is terminated by the dual action of beta-adrenergic receptor kinase and beta-arrestin G proteins have intrinsic GTPase activity that is time-sensitive Cyclic AMP (cAMP) inside the cell is broken down by phosphodiesterase enzymes Concentration of the receptor's ligand in the extracellular fluid decreases

Inactivation of the receptor by phosphatase enzymes Explanation: In this question, all of the answer choices will be true except for one. Therefore, we'll need to consider each answer choice, one by one, in order to determine whether it is a true statement. First, let's briefly recall the basics of G protein-coupled receptors (GPCRs). These receptors are located on the cell membrane, and work by binding to ligands on the extracellular side. This binding induces a conformational change in the receptor, which then activates a G protein on the inner membrane. This activated G protein becomes active by shedding the GDP it has bound, and in exchange it binds to a new GTP molecule. This newly activated G protein then goes on to activate another enzyme found within the cell membrane, called adenylyl cyclase. This enzyme, when activated this way, catalyzes the transformation of ATP into cyclic AMP (cAMP). This cAMP, in turn, acts as a second messenger and, in doing so, activates protein kinase A (PKA). PKA then goes on to phosphorylate a wide range of target proteins, which ultimately leads to a cellular response. In addition, there are other types of GPCRs that lead to a different kind of signal transduction cascade. This alternative pathway involves the signaling molecules inositol triphosphate (IP3), diacylglycerol (DAG), and protein kinase C (PKC). But for the purposes of this question, we will focus on the one explained above. G Protein cascades are one type of transduction pathway, and just like any other biological process, it is important that it is regulated. Therefore, when turn on, there needs to also be mechanisms in place to turn it off. One of the ways in which the cascade is turned off is through the innate GTPase activity of the G proteins themselves. After a certain amount of time has passed, these G Proteins are able to hydrolyze their bound GTP into GDP, and in doing so, they become inactivated. Another method used to turn off the pathway is through the combined action of beta-adrenergic receptor kinase and beta-arrestin. In this case, beta-adrenergic receptor kinase phosphorylates the receptor. This, in turn, attracts beta-arrestin to the receptor, which then physically blocks the receptor from interacting with G Proteins. Additionally, the pathway can be turned once the extracellular ligand has fallen to a low concentration. Yet another way that the pathway can be turned off is by the reduction in the second messenger cAMP. This is accomplished by the activity of a class of enzymes called the phosphodiesterases. And lastly, phosphatases are enzymes which remove phosphate groups from their targets. As was mentioned above, the phosphorylation of GPCRs results in their inactivation. Therefore, if phosphate groups were to be removed from them, this would tend to have the opposite effect of activating them. Therefore, the action of phosphatases on GPCRs would not turn them off.

Which of the following is false about integrin structure and function? Possible Answers: Integrins bind a cytoskeleton to the extracellular matrix. Integrins are central to blood clotting. Integrins can set off signaling pathways in the cell, indicating the nature of the extracellular matrix. Typically, integrins are attached to actin or intermediate filaments. Integrins are made of a single subunit.

Integrins are made of a single subunit. Explanation: Integrins have two subunits, alpha and beta. They do indeed bind the cell's cytoskeleton to its matrix, and can indicate to the cell the nature of that matrix. Integrins attach to a cell's actin and intermediate filaments. Blood platelets contain integrins, which bind proteins, like fibrinogen, in the matrix. This permits blood clotting, and the absence of certain integrins can cause a pathology in which people's blood does not clot well.

How does the sodium-potassium pump accomplish its function of maintaining the electrochemical potential across a cell membrane?

It actively moves three sodium ions out of the cell and two potassium ions in, both against their concentration gradients

Which of the following correctly characterizes a G protein-coupled receptor (GPCR)? Possible Answers: It responds to insulin It is only found in the central nervous system It responds to changes in voltage across the membrane It can lead to a decrease in calcium levels in the cell

It can lead to a decrease in calcium levels in the cell Explanation: G protein coupled-receptors can be classified into three categories: Gq, Gi, or Gs. Gq and Gs are stimulatory receptors whereas Gi is inhibitory. Gq activates the phospholipase C (PLC) pathway and Gs activates the cAMP and, subsequently, protein kinase C (PKC) pathway. Gi, on the other hand, inhibits several signaling cascades in the cells. One of the prominent effects of Gi receptor is that it inhibits the increase of calcium levels intracellularly. Recall that calcium levels are kept at a very low concentration inside the cell. Upon activation of certain pathways, calcium influx can occur from either the outside of the cell or from within the organelles (such as rough endoplasmic reticulum). This will lead to an increase in the cytoplasmic calcium levels. Increase in cytoplasmic calcium levels will initiate several pathways inside the cell. To prevent overactivity of these pathways, calcium levels are closely controlled within the cell. One way to regulate the calcium levels is by the activation of Gi receptor. Insulin binds to receptor tyrosine kinases, G protein coupled receptors are found throughout the body (not just the central nervous system), and GPCR's respond to ligand binding, not voltage changes.

The sodium-potassium pump is used in many different cells to control the concentration and movement of ions across the membrane. Which of the following is true about the sodium-potassium pump? Possible Answers: It uses ATP to bring sodium into the cell It uses ATP to exchange one potassium ion and one sodium ion It is active transport, effectively making the cytosol more negative It is passive transport, making the cytosol polarize The pump allows sodium and potassium to flow down their electrochemical gradients

It is active transport, effectively making the cytosol more negative Explanation: Many of the distractors have partially correct statements. In full, the sodium-potassium ATPase pump is an active exchanger, meaning it is a transporter that uses ATP to move two different ions across the membrane. In this case, the transporter hydrolyzes ATP to move 3 sodium ions out of the cell and 2 potassium ions into the cell. This means that with every transport the cell looses a negatively charged cation, making the cytosol a little more negatively charged. The sodium-potassium pump often moves the molecules against their concentration gradients.

Receptor tyrosine kinases (RTKs) transduce extracellular signals into intracellular signaling cascades. This is possible because RTKs have an extracellular ligand binding domain to sense ligands outside of the cell, a transmembrane domain that spans the cell membrane, and an intracellular domain that activates pathways within the cell. Which of the following best describes the mechanism by which the cytosolic domains of RTKs activate downstream signaling cascades? Possible Answers: Ligand binding to the extracellular RTK domain facilitates phosphorylation of the RTK intracellular domain by protein kinase A, which is required for all downstream signaling cascades to be activated. Ligand binding to the extracellular RTK domain permits the RTK to interact with other receptors on other cells, triggering bidirectional signaling cascades. Ligand binding to the extracellular RTK domain triggers cleavage of the intracellular domains, which then act as soluble second messengers to activate protein kinases. Ligand binding to the extracellular RTK domain stimulates dimerization of RTKs, and the cytosolic domains cross-phosphorylate one another to activate the kinase domains. Ligand binding to the extracellular RTK domain triggers an influx of calcium through calcium-channels, activating second messengers within the cell.

Ligand binding to the extracellular RTK domain stimulates dimerization of RTKs, and the cytosolic domains cross-phosphorylate one another to activate the kinase domains. Explanation: Ligand binding stabilizes the dimerization of cytosolic domains of RTKs, and the intracellular domains can trans-phosphorylate one another (autophosphorylate) to activate the kinase domains. While there are other mechanisms of activation for RTKs, none of the other answers provide a correct mechanism for this activation.

Which of these transporters involves the formation of a high energy intermediate? Possible Answers: GLUT1 transporter Lactose permease Calcium-hydrogen ATPase Sodium-potassium ATPase More than one of these answers

More than one of these answers Explanation: The sodium-potassium ATPase and the calcium-hydrogen ATPase (active transporters) are both correct and form high energy aspartyl phosphate intermediates inside the cell.

A researcher is analyzing the effects of a receptor on a cell. He observes that the receptor autophosphorylates itself at certain amino acid residues. What can you conclude about this receptor? Possible Answers: A kinase will be activated More than one of these are correct Aspartic acid residues are phosphorylated It will not lead to an increase in protein kinase C levels

More than one of these are correct Explanation: There are several types of receptors found on a cell membrane. These receptors function to transduce an external signal (in the form of a ligand or voltage changes) into an intracellular signal. The question states that the receptor autophosphorylates itself. This means that the receptor must have kinase activity. Recall that, upon activation (by ligand binding), receptor tyrosine kinases self phosphorylate their tyrosine residues; therefore, the receptor stated in this question is a receptor tyrosine kinase. After auto-phosphorylation, the receptor tyrosine kinase will phosphorylate other molecules (kinase) that will lead to a signaling cascade. As mentioned, tyrosine residues are phosphorylated, not aspartic acid residues.

G protein-coupled receptor is an example of __________ ion channel and the insulin receptor is an example of __________ ion channel. Possible Answers: voltage-gated . . . voltage-gated None of these ligand-gated . . . voltage-gated ligand-gated . . . ligand-gated

None of these Explanation: G protein-coupled receptor (GPCR) is a receptor that is activated by the binding of a ligand; however, it acts through a second messenger molecule (cAMP). This means that the activation of GPCR activates cAMP, which activates subsequent signaling pathways. GPCRs are not involved in the influx and efflux of ions; therefore, they aren't ion channels. Insulin receptor is a type of a receptor tyrosine kinase. Upon binding, insulin activates the RTK which eventually leads to activation of genes for the glucose transporters. This increases the glucose uptake by the cells. Similar to GPCR's, insulin receptor does not allow movement of ions across the membrane; therefore, it isn't an ion channel.

Which of the following is true regarding second messengers? Possible Answers: They are activated by voltage gated ion channels None of these They are activated by ligand gated ion channels They are activated by ligand gated and voltage gated ion channels

None of these Explanation: Signaling receptors can be divided into two categories: ion channels and second-messenger utilizing receptors. Ion channels are activated by voltage changes (voltage-gated) or ligand binding (ligand-gated) and they tend to increase the flow of ions into and outside of cell. Receptors, such as G protein-coupled receptors, are activated by ligand binding; however, they signal the cell by activating second messenger molecules such as cAMP.

A bacterium is often recognized and attacked by the immune cells. What is true regarding this process? Possible Answers: Toll-like receptors (TLRs) on the bacteria signal and recruit immune cells None of these Peptidoglycan is a molecule recognized by immune cells Toll-like receptors (TLRs) on the bacteria signal and recruit immune cells and peptidoglycan is a molecule recognized by immune cells

Peptidoglycan is a molecule recognized by immune cells Explanation: Toll-like receptors are special molecules that recognize specific portions of pathogens called PAMPs (pathogen associated molecular patterns). The toll-like receptors on the immune cells recognize PAMPs on the pathogen. One of the most common PAMPs recognized by toll-like receptors is peptidoglycan on the cell walls of the bacteria.

Protein-tyrosine kinase activation can result in the activation of two classical second messengers, inositol triphosphate (IP3) and diacylglycerol (DAG). These molecules are produced as a result of a hydrolysis reaction that is stimulated by protein-tyrosine kinase activation. What is the enzyme that catalyzes this hydrolysis reaction, and what molecule is cleaved into IP3 and DAG? Possible Answers: Phospholipase C, PIP2 Phospholipase C, Ca2+ Protein kinase A, diglyceride Protein kinase C, PIP2 Protein kinase B, phosphatidylcholine

Phospholipase C, PIP2 Explanation: In this specific pathway, protein-tyrosine kinase phosphorylation activates phospholipase C (PLC), which then catalyzes the hydrolysis of PIP2, a membrane phospholipid, into IP3 and DAG. IP3 and DAG then go on to activate second messenger cascades. Protein kinases can be activated by tyrosine kinases, but PLC is the enzyme specifically required for the IP3/DAG cascade.

cAMP is one of the most fundamentally important 2nd degree messengers in the cell, released by a variety of receptors. In a phosphorylation system, what is the direct purpose of cyclic AMP, what does protein does this secondary messenger activate? Possible Answers: Glycogen synthase Protein kinase A Phosphoprotein phosphatase inhibitor Glycogen phosphorylase Phosphorylase kinase B

Protein kinase A Explanation: A phosphorylation cascade, involves many different steps and complicated interactions between kinases, phosphorylases, and phosphatases. In this case, the enzymes mentioned relate to the phosphorylation and dephosphorylation cascade involved with glycogen synthesis and degradation. When a beta-adrenergic receptor or glucagon receptor is activated, two types of G-protein couple receptors, a G-protein is phosphorylated and disassociates GTP to act upon the enzyme, Adenylate cyclase, to synthesize cylic AMP (cAMP) from ATP. This first step following the release of cAMP is that it acts upon protein kinase A by attaching to its two R subunits (requiring 4 cAMP) while releasing two C subunits. The C subunits function as other chemical messengers in the cell, acting upon multiple different enzymes to ultimately increase the rate of glycogen degradation and decrease the rate of glycogen synthesis.

Which of the following correctly matches the SH2 (Src Homology 2) and SH3 (Src Homology 3) domains with their residues? Possible Answers: SH2 domains bind phosphotyrosine, SH3 domains bind phosphoserine SH2 domains bind phosphotyrosine, SH3 domains bind proline-rich sequences SH2 domains bind phosphoserine, SH3 domains bind phosphothreonine SH2 domains bind phosphothreonine, SH3 domains bind phosphotyrosine

SH2 domains bind phosphotyrosine, SH3 domains bind proline-rich sequences Explanation: SH2 and SH3 domains are Src homology domains that interact with insulin receptor tyrosine kinase substrates. They are especially important in the Ras-activated MAP kinase cascade. SH2 domains, because of their deep positive arginine pockets, tightly bind phosphotyrosine residues but not phosphoserine and phosphothreonine residues.

The sodium-potassium pump is an antiporter that moves sodium ions out of the cell and potassium ions into the cell. This pumping action requires ATP. What can you conclude about the electrochemical gradient of sodium?

Sodium concentration is higher outside the cell because the pump drives sodium ions against their electrochemical gradient

Second messenger cascades are frequently initiated by activation of a G protein-coupled receptor (GPCR). Ligand binding to the extracellular domain of the GPCR triggers a conformation change in the GPCR that permits activation and dissociation of the G protein to which it is associated. What is the biochemical change catalyzed by the activated GPCR that permits activation of its associated G protein? Possible Answers: The GPCR breaks covalent bonds between the intracellular domain and the G protein The GPCR exchanges the G protein's bound GDP for a GTP The GPCR phosphorylates protein kinases, which phosphorylate and activate the G protein The GPCR exchanges the G protein's bound GDP for a GMP The GPCR opens ion channels, and influx of calcium activates the G protein

The GPCR exchanges the G protein's bound GDP for a GTP Explanation: Once the conformation change has been induced by ligand binding, the GPCR can act as a guanine exchange factor (GEF) which exchanges out a bound GDP (lower energy) on the G-protein for a GTP (higher energy). This triggers the dissociation of the G-protein, and it goes on to activate various second messenger cascades within the cell. Generally, addition of phosphate groups in biochemistry signals "activation," and removal triggers "deactivation."

Which of the following statements about the adenylate cyclase signaling system is incorrect? Possible Answers: The Gq subunit stimulates adenlyate cyclase to produce cAMP. Toxins such as cholera and pertussis can inhibit certain steps in the G protein pathway. cAMP-phosphodiesterases limit second messenger activity. Adenylate cyclase is involved in the initial pathway that activates protein kinase A by binding four cAMP molecules. Mammalian adeylate cyclases have nine different isoforms, and the structure is predicted to be six transmembrane helices.

The Gq subunit stimulates adenlyate cyclase to produce cAMP. Explanation: The Gq Gs-alpha bound to GTP dissociates and stimulates adenlyate cyclase to produce cAMP. (Gq is involved in the phosphoinositide pathway, not the adenylate cyclase pathway.) All other answer choices are correct with regards to the adenylate cyclase signaling system.

Which of the following correctly describes activation of a G protein? Possible Answers: The beta unit dissociates from the alpha/gamma unit upon conversion of GTP to GDP The alpha subunit dissociates from the beta/gamma unit upon conversion of GTP to GDP The alpha subunit dissociates from the beta/gamma unit upon conversion of GDP to GTP The heterotrimeric G protein remains intact as a single unit, but GTP is converted to GDP The beta unit dissociates from the alpha/gamma unit upon conversion of GDP to GTP

The alpha subunit dissociates from the beta/gamma unit upon conversion of GDP to GTP Explanation: In its unactivated state, a G protein is present as a heterotrimer consisting of an alpha, a beta, and a gamma subunit. This heterotrimer is bound to GDP. Upon activation by conversion of GDP to GTP, the G protein will dissociate into an alpha subunit separated from the beta and gamma unit (these two are still connected).

How is the activity of a G protein stopped? Possible Answers: GTP dissociates completely from the G protein reverting it back to its inactive state A GTPase enzyme comes in contact with the G protein, which converts GTP back to GDP The gamma subunit of a G protein has an intrinsic GTPase, which converts GTP back to GDP The alpha subunit of a G protein has an intrinsic GTPase, which converts GTP back to GDP The beta subunit of a G protein has an intrinsic GTPase, which converts GTP back to GDP

The alpha subunit of a G protein has an intrinsic GTPase, which converts GTP back to GDP Explanation: The alpha subunit of a G protein has intrinsic GTPase activity that, although slow, will automatically convert GTP back to GDP when the action of the G protein has finished.

In a G protein-coupled receptor, the activation of an inhibitory G protein will lead to which of the following? Possible Answers: Adenyl cyclase hydrolysis of ATP The activation of adenylyl cyclase The decrease in cAMP An inactivated alpha subunit of the G protein Downstream activation of PKA

The decrease in cAMP Explanation: With an inhibitory G protein, the binding of a ligand and stimulation of the receptor will activate the alpha subunit of the G protein, however since it is an inhibitory G protein, it will not go on to activate adenyl cyclase. With no activation of Adenyl cyclase it will lead to decrease cAMP and other secondary messengers.

At the distal end of the axon shown in Figure 1, what process directly drives the fusion of synaptic vesicles to discharge neurotransmitter into the synaptic cleft?

The influx of calcium at the synaptic terminal

.What is one of the main purposes of second messenger molecules? Possible Answers: They allow a single signal to cause endless, unceasing production of some final product They allow receptors to be receptive to multiple types of ligands They allow for signifiant amplification of a signal within a cell They allow ligands to bind to multiple types of receptors They allow for the production of only one kind of molecule

They allow for signifiant amplification of a signal within a cell Explanation: When a ligand binds to its associated receptor, the signal is passed into the cell and on to a distinct final molecule (often DNA transcription factors). Second messengers allow for significant amplification of a single ligand/receptor signal in order to cause mass change within a cell, and therefore within the body

Which of the following is true regarding ligand-gated ion channels? Possible Answers: They transport uncharged and charged molecules They facilitate the repolarization of a nerve They are found on phospholipid bilayers They respond to changes in voltage

They are found on phospholipid bilayers Explanation: Ligand-gated ion channels are activated by a ligand. Upon activation, the ion channels open and allow for passage of ions through the membrane. They are usually found on membranes such as plasma membrane and organelle membranes and facilitate the exchange of ions between cytoplasm and the extracellular matrix (or inside of organelles). Since all membranes found in a cell are phospholipid bilayers, ligand-gated ion channels are found on phospholipid bilayers.

Where do protein kinases most commonly add phosphate groups from ATP for signaling purposes? Possible Answers: To the nitrogen on arginine, histidine, and lysine To the hydroxyl group of tyrosine, threonine, or serine To the carboxyl group on aspartic and glutamic acids To the −SH group on cysteine To the sulfur on methionine

To the hydroxyl group of tyrosine, threonine, or serine Explanation: The most common point of transfer of an ATP phosphate group is to the hydroxyl of tyrosine, serine, and threonine. Tyrosine and serine/threonine-specific kinases, in particular, help regulate signal transduction. As for the other amino acids, another kinase that sometimes appears is a histidine kinase, mostly in prokaryotes. Sulfur, nitrogen, and carboxyl groups are not typical targets for phosphorylation within proteins for signaling purposes.

Which of the following is false about G protein-linked receptors? Possible Answers: Their polypeptide chain crosses the cellular membrane seven times. G proteins are found on the cellular membrane, on the side of the cytosol. When the receptor is activated, the β subunit releases GDP and binds to GTP, causing β and γ to come apart. G proteins have three subunits, α, β, and γ. Among all the cell surface receptors, G protein-linked are the most common in eukaryotes.

When the receptor is activated, the β subunit releases GDP and binds to GTP, causing β and γ to come apart. Explanation: G protein-linked receptors are, indeed, the most commonly found in prokaryotes, and their polypeptide chain crosses the membrane seven times -- hence the alternate name, serpentine receptor. The G-protein is bound to the interior of the plasma membrane, sometimes, at least, in a complex with the receptor. G proteins do have three subunits, α, β, and γ. However, it is α that releases GDP and binds GTP, dissociating the protein, with two resulting parts, an α and a βγ complex.

Second messengers are __________ by receptor tyrosine kinase pathway and are __________ by voltage gated ion channels. Possible Answers: not activated . . . activated activated . . . activated activated . . . not activated not activated . . . not activated

activated . . . not activated Explanation: Receptor tyrosine kinase pathway utilizes second messenger molecules to activate molecules in the cell that, subsequently, activate cellular mechanisms. Ion channels allow for flow of ions between membranes; they do not directly activate second messenger molecules.

Which of the following is not a second messenger produced by the phosphoinositide pathway? Possible Answers: cAMP Ca2+ IP3 DAG (diacylglycerol)

cAMP Explanation: cAMP is a second messenger produced by the adenylate cyclase pathway (among other pathways).

How does cAMP exert its effects within a cell? Possible Answers: cAMP acts directly on transcription factors, which then go on to cause alterations in gene expression cAMP activates protein kinase A, which then acts upon other target molecules cAMP is hydrolyzed to ATP, which phosphorylates target molecules cAMP acts directly upon DNA to cause alterations in gene expression cAMP closes chloride channels, causing a change in the cellular membrane potential

cAMP activates protein kinase A, which then acts upon other target molecules Explanation: After adenylate cyclase converts ATP to cAMP, this second messenger goes on to bind to protein kinase A. Unactivated protein kinase A requires cAMP in order to become activated, at which point it can phosphorylate certain threonine and serine residues on target molecules.

How does protein kinase A become activated? Possible Answers: cAMP dissociates from the catalytic subunits which allows them to be active cAMP binds to its regulatory subunits and to its catalytic subunits causing dissociation of the now activated catalytic subunits cAMP binds only to its catalytic subunits causing their dissociation from the regulatory subunits cAMP binds only to its regulatory subunits causing dissociation of its catalytic subunits cAMP dissociates from the regulatory subunits which allows the catalytic subunits to be active

cAMP binds only to its regulatory subunits causing dissociation of its catalytic subunits Explanation: In order for protein kinase A to become activated, cAMP must bind to it. PKA has a structure composed of two regulatory subunits and two catalytic subunits all bound together. The catalytic units are active on their own, so in order to work they must simply become dissociated from the regulatory subunits. Thus, cAMP will bind to only the regulatory subunits of PKA which then allows dissociation of the already catalytic subunits.

The cell body associated with the axon depicted in Figure 1 takes in neural impulses from a variety of other neurons. A tract that carries such impulses into the cell body is __________.

called a dendrite, and is often present in greater numbers on a single cell than the single axon

Cyclic GMP (cGMP) is produced when the enzyme __________ converts the precursor GTP into cGMP. The reaction involves the removal of __________ from the GTP precursor. Possible Answers: cGMP protein kinase . . . one phosphate group guanylyl cyclase . . . two phosphate groups guanylyl cyclase . . . one phosphate group cGMP protein kinase . . . two phosphate groups adenylyl cyclase . . . two phosphate groups

guanylyl cyclase . . . two phosphate groups Explanation: Guanylyl cyclase is the enzyme responsible for catalyzing this reaction, and the reaction involves removing two phosphate groups from guanosine triphosphate to generate cyclic guanosine monophosphate. Adenylyl cyclase performs a similar reaction but the substrate is adenosine triphosphate and the product is cyclic adenosine monophosphate. cGMP protein kinase is a target that is activated by cGMP, but is not involved in this reaction.

The primary purpose of the sodium/potassium pump is to __________.

xport three sodium ions, import two potassium ions, and establish cell membrane resting potential Explanation: Na+/K+ ATPase always exports three sodium ions out of the cell and imports two potassium ions into the cell. The export of three positively charged sodium ions for the import of only two positively charged potassium ions results in a net -70mV charge across the cell membrane, which is known as the cell membrane resting potential.