10. Cell Signaling

Signal Amplification

Suppose you were to model amplification by the phosphorylation cascade in Figure 11.16, using a penny for each kinase 1, a nickel for each kinase 2, and a dime for each kinase 3. Also suppose that Ras and each of the kinases can activate 10 proteins. How much money would you need to construct your model?

 No. Sometimes it inactivates a protein, but not always. 

 No. G-protein-coupled receptors are not activated by phosphorylation. 

 is accomplished by protein phosphatases 

 No. Protein phosphatases remove phosphate groups from proteins. 

 No. This is often the case, but not always. 

 can either activate or inactivate a protein 

Phosphorylation does not always have the same effects.

Phosphorylation __________.

Are enzymes that can turn proteins “on” and/or “off” through changes in phosphorylation.

Are enzymes that can turn proteins “on” and/or “off” through changes in proton concentrations. 

Kinases and phosphatases are essential to the cell because they:a) Are enzymes that synthesize proteins.b) Are enzymes that degrade proteins.c) Are enzymes that can turn proteins “on” and/or “off” through changes in phosphorylation.d) Are enzymes that can turn proteins “on” and/or “off” through changes in proton concentrations.e) None of the above.

 is always present at high levels in the cytosol; is present at low levels in the absence of a signal 

 No. Adenylyl cyclase has to be activated by an appropriate signal for cAMP to be present. 

 is stored in the endoplasmic reticulum; is never stored in the cell 

No. Ca2+ is stored in the ER, but cAMP is not stored in the ER.

 is tyrosine-kinase-receptor linked; is G-protein-receptor linked 

 No. Calcium and cAMP are both second messengers involved in G-protein-mediated signaling pathways. 

 enters the cell via a transmembrane protein channel; enters the cell by diffusing across the plasma membrane 

 No. cAMP does not enter the cell via a transmembrane protein channel. It is synthesized by adenylyl cyclase in the cytoplasm. Calcium enters the cell through specific channels and is stored in the endoplasmic reticulum. 

 is synthesized by an enzyme in response to a signal; is released from intracellular stores 

Consider the sources of cAMP and Ca2+.

A difference between the mechanisms of cAMP and Ca2+ in signal transduction is that cAMP __________ and Ca2+ __________.

Phosphorylation Cascades

 An increase in the numbers of phosphorylated proteins in the cell 

 No. Consider what is required for kinases to phosphorylate proteins. 

 An increase in anabolic cellular reactions 

 No. Most anabolic reactions are coupled to the hydrolysis of ATP. Because ATPgammaS cannot be hydrolyzed, there could not be an increase in ATP-dependent anabolic reactions. 

 No. Cell division requires cell growth, which is the sum of many anabolic reactions&#151;most such reactions cannot work if ATP cannot be hydrolyzed. 

 Two of the listed responses would be expected. 

 No. Only one of the listed responses could reasonably be expected given the information that is presented. 

 A decrease in phosphorylated proteins in the cell 

Consider which kinds of proteins use ATP.

ATPgammaS is a form of ATP that cannot be hydrolyzed by enzymes. If this compound were introduced to cells so that it replaced the normal ATP present in the cell, which of the following would you predict?

Calcium & IP3 Pathway

 an increase in the amount of cAMP present in the cell 

 No. That would result from a mutation that increased the activity of adenylyl cyclase. 

 No. Activation of protein kinase A requires cAMP, and the mutation described reduces the amount of cAMP being produced in the cell. 

 reduced binding of adenylyl cyclase to protein kinase A 

 No. Adenylyl cyclase converts ATP to cAMP, which activates protein kinase A. Adenylyl cyclase does not directly act on protein kinase A. 

 increased binding of adenylyl cyclase to the G protein that activates it 

 No. Changing the catalytic activity of adenylyl cyclase by mutating the active site of the enzyme should have no effect on the interaction between it and a G protein that binds to it. 

Consider the function of adenylyl cyclase.

A mutation in the active site of adenylyl cyclase that inactivates it would most likely lead to __________.

The activation of receptor tyrosine kinases is characterized by
a. dimerization and phosphorylation.
b. dimerization and IP3 binding.
c. a phosphorylation cascade.
d. GTP hydrolysis.

 No. Many cAMPs are formed; thus, the signal is not reduced. 

 the number of molecules involved decreases 

 No. Many cAMPs are formed; thus, the number of molecules does not decrease. 

 the number of molecules involved remains constant 

 No. Many cAMPs are formed; thus, the number of molecules involved does not remain constant. 

 No. This signal-transduction pathway stimulates the breakdown of glycogen into glucose. 

Consider that each adenylyl cyclase molecule can catalyze the formation of many cAMPs.

In liver cells, epinephrine stimulates the breakdown of glycogen. As the signal-transduction pathway progresses, __________.

Moss sperm are motile and capable of swimming short distances to fertilize an egg. However, it was unknown until recently how sperm make their way from male to female gametophytes that may be separated by a distance of several centimeters or more.

Animals are responsible for pollinating many flowering plants. Did animal-mediated fertilization originate with flowering plants, or was this mode of sperm dispersal likely in place before the origin of flowering plants? Explain.

 No. In animals, glycogen is the storage form of carbohydrate. It is not a second messenger. 

 No. Transfer RNA is important for the synthesis of proteins. It is not a second messenger. 

 No. Epinephrine is a hormone. It is not a second messenger. 

 No. Glucose is a sugar that cells utilize as a source of energy. It is not a second messenger. 

Sutherland discovered the importance of this substance in his studies of the effects of epinephrine on glycogen breakdown in liver cells.

In eukaryotic cells, which of the following is a second messenger that is produced as a response to an external signal such as a hormone?

Which observation suggested to Sutherland the involvement of a second messenger in epinephrine’s effect on liver cells?
a. Enzymatic activity was proportional to the amount of calcium added to a cell-free extract.
b. Receptor studies indicated that epinephrine was a ligand.
c. Glycogen breakdown was observed only when epinephrine was administered to intact cells.
d. Glycogen breakdown was observed only when epinephrine and glycogen phosphorylase were mixed.

Amplification in Signal Transduction pathways

Consider this pathway: epinephrine → G protein-coupled receptor → G protein → adenylyl cyclase → cAMP. Identify the second messenger.
a. cAMP
b. G protein
c. GTP
d. adenylyl cyclase

Adenylyl Cyclase - cAMP Pathway || Gs and Gi Protein Pathway

They phosphorylate proteins involved in signal transduction or cellular response.

They activate protein kinases by phosphorylation.

They regulate the function of proteins involved in signal transduction pathways or cellular response.

What role do phosphatases play in signal transduction pathways?a) They phosphorylate proteins involved in signal transduction or cellular response.b) They activate protein kinases by phosphorylation.c) They amplify the signal molecule.d) They regulate the function of proteins involved in signal transduction pathways or cellular response.

 No. Even though they are small, second messengers cannot penetrate the hydrophobic core of the plasma membrane. 

 No. This would imply that they were able to cross membranes freely, a difficult task for a polar molecule or ion. 

 move from substrate to substrate during a phosphorylation cascade 

 No. During a cascade, each substrate becomes the activator for the next substrate. A second messenger would be needed to start the process but would then participate no further. 

 cross the nuclear membrane and interact with DNA 

 No. Second messengers do not interact with DNA. 

 rapidly move throughout the cell by diffusion 

How do these properties affect the ability to move within a cell?

Second messengers tend to be water-soluble and small. This accounts for their ability to __________.

Allow proteins to be easily activated by adding or removing a phosphate group.

Allow proteins to be easily deactivated by adding or removing a phosphate group.

Phosphorylation cascades are useful signal transduction pathways because they ________.a) Allow proteins to be easily activated by adding or removing a phosphate group.b) Allow proteins to be easily deactivated by adding or removing a phosphate group.c) Amplify the original signal many times.d) All of the above.

Receptors: Signal Transduction and Phosphorylation Cascade

 muscle cells lack the appropriate membrane receptor 

 No. However, a missing or defective receptor would certainly result in a disease process. 

 nerve cells lack the ability to produce cAMP 

 No. This disorder is not related to the production of cAMP. 

 G proteins are unable to phosphorylate GDP 

 No. G proteins are not involved with the disorder, and G proteins normally hydrolyze GTP to terminate their activation rather than phosphorylating GDP. 

 the endoplasmic reticulum is unable to store calcium 

 No. This disorder is not related to calcium concentrations within the cell. 

 a multifunctional relay protein involved with the proliferation of immune cells is defective 

Immune cell behavior is affected.

In the inherited disorder Wiskott-Aldrich syndrome, __________.

 No. Protein kinase A phosphorylates proteins. 

 No. Calcium acts as a second messenger. 

No. However, the molecule from which IP3 is derived is also involved in the formation of DAG.

 No. Adenylyl cyclase is responsible for producing the second messenger cAMP. 

 the cleavage of a specific phospholipid in the plasma membrane 

Something else is cleaved to produce it.

IP3 (inositol trisphosphate) is produced as a result of __________.

 No. Review the section on second messengers. 

No. Phospholipase C cleaves PIP2 into IP3 and DAG.

No. IP3 and DAG are both products of the cleavage of PIP2 by phospholipase C. Neither activates the other.

IP3 (inositol trisphosphate) stimulates the release of calcium from the ER.

IP3 (inositol trisphosphate) acts by __________.

Moss sperm are motile and capable of swimming short distances to fertilize an egg. However, it was unknown until recently how sperm make their way from male to female gametophytes that may be separated by a distance of several centimeters or more.

Besides springtails, are there other ways moss sperm may be transferred from male to female gametophytes?

Protein phosphorylation is commonly involved with all of the following except
a. activation of receptor tyrosine kinases.
b. activation of protein kinase molecules.
c. activation of G protein-coupled receptors.
d. regulation of transcription by signaling molecules.

 No. Although this is true, there is a better choice. 

 All of the listed responses are correct. 

Review the relationships between the major types of receptors and second messengers.

During the transduction of a signal, one molecule or ion may be closely associated with the activity of another. Which of the following pairs correctly combines two associated molecules?

 No. Dehydrogenases are involved with redox reactions. They participate in the movement of electrons and hydrogen. 

 No. Protein phosphatases catalyze the removal of a phosphate group from another protein. 

 No. Peptidases are enzymes that hydrolyze peptide bonds. 

 No. A cyclase is an enzyme, such as adenylyl cyclase, that converts its substrate into a ring structure. 

About 2% of our genes are thought to code for these.

The general name for an enzyme that transfers phosphate groups from ATP to a protein is __________.

Steroid hormones, like most lipid-soluble signaling molecules, are processed directly. How does the absence of a signal transduction cascade in the processing of steroid hormones affect (b) signal regulation?

Angiosperms such as grasses, oaks, and maples are wind pollinated. The ancestors of these subgroups were probably pollinated by insects, however. As an adaptive advantage, why might a species “revert” to wind pollination? (Hint: Think about the costs and benefits of being pollinated by insects versus wind.) Why is it logical to observe that wind-pollinated species usually grow in dense stands containing many individuals of the same species? Why is it logical to observe that in wind-pollinated deciduous trees, flowers form very early in spring—before leaves form?

 No. Phosphodiesterase inactivates cAMP. 

 No. Receptor tyrosine kinases reside in the plasma membrane as integral membrane proteins. 

 No. The production of cAMP is a result of G protein activation. 

 No. Adenylyl cyclase converts ATP to cAMP. 

This is a serine/threonine kinase.

The molecule cAMP usually directly activates __________.

Animation: Signal Transduction Pathways

 No. The molecule cAMP is a second messenger. It does not donate phosphate groups. 

 No. Protein kinases transfer phosphate groups from one molecule to another. 

 No. GTP is important for the activation of G proteins in signal transduction pathways. 

This molecule is the primary energy-transferring molecule in the cell.

The source of phosphate for a phosphorylation cascade is __________.

Cell signalling: kinases & phosphorylation

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