Essential Cell Biology

Bruce Alberts, Dennis Bray, Karen Hopkin

Chapter 16

Cell Signaling - all with Video Answers

Educators

Chapter Questions

Problem 1

To remain a local stimulus, paracrine signal molecules must be prevented from straying too far from their points of origin. Suggest different ways by which this could be accomplished. Explain your answers.

Sidharth Anand

Sidharth Anand

Numerade Educator

Problem 2

Consider the structure of cholesterol, a small hydrophobic molecule with a sterol backbone similar to that of three of the hormones shown in Figure $16-9$, but possessing fewer polar groups such as $-\mathrm{OH},=\mathrm{O},$ and $-\mathrm{COO}^{-}$. If cholesterol were not normally found in cell membranes, could it be used effectively as a hormone if an appropriate intracellular receptor evolved?

Sidharth Anand

Numerade Educator

Problem 3

In principle, how might an intracellular signaling protein amplify a signal as it relays it onward?

Sidharth Anand

Numerade Educator

Problem 4

The signaling mechanisms used by a steroid-hormone-type nuclear receptor and by an ionchannel-coupled receptor are relatively simple as they have few components. Can they lead to an amplification of the initial signal, and, if so, how?

Sidharth Anand

Numerade Educator

Problem 5

GPCRs activate G proteins by reducing the strength of GDP binding to the G protein. This results in rapid dissociation of bound GDP, which is then replaced by GTP, because GTP is present in the cytosol in much higher concentrations than GDP. What consequences would result from a mutation in the $\alpha$ subunit of a G protein that caused its affinity for GDP to be reduced without significantly changing its affinity for GTP? Compare the effects of this mutation with the effects of cholera toxin.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 6

Explain why cyclic AMP must be broken down rapidly in a cell to allow rapid signaling.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 7

Why do you suppose cells have evolved intracellular $\mathrm{Ca}^{2+}$ stores for signaling even though there is abundant extracellular $\mathrm{Ca}^{2+}$ ?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 8

One important feature of any intracellular signaling pathway is its ability to be turned off. Consider the pathway shown in Figure $16-31 .$ Where would off switches be required? Which ones do you suppose would be the most important?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 9

Would you expect to activate RTKs by exposing the exterior of cells to antibodies that bind to the respective proteins? Would your answer be different for GPCRs? (Hint: review Panel $4-3$, on pp. $164-165,$ regarding the properties of antibody molecules.)

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 10

If some cell-surface receptors, including Notch, can rapidly signal to the nucleus by activating latent transcription regulators at the plasma membrane, why do most cellsurface receptors use long, indirect signaling cascades to influence gene transcription in the nucleus?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 11

Which of the following statements are correct? Explain your answers.
A. The extracellular signal molecule acetylcholine has different effects on different cell types in an animal and often binds to different cell-surface receptor molecules on different cell types.
B. After acetylcholine is secreted from cells, it is long-lived, because it has to reach target cells all over the body.
C. Both the GTP-bound $\alpha$ subunits and nucleotide-free $\beta \gamma$ complexes-but not GDP-bound, fully assembled G proteins-can activate other molecules downstream of GPCRs.
D. $\mathrm{IP}_{3}$ is produced directly by cleavage of an inositol phospholipid without incorporation of an additional phosphate group.
E. Calmodulin regulates the intracellular $\mathrm{Ca}^{2+}$ concentration.
F. Different signals originating from the plasma membrane can be integrated by cross-talk between different signaling pathways inside the cell.
G. Tyrosine phosphorylation serves to build binding sites for other proteins to bind to RTKs.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 12

The Ras protein functions as a molecular switch that is set to its "on" state by other proteins that cause it to expel its bound GDP and bind GTP. A GTPase-activating protein helps reset the switch to the "off" state by inducing Ras to hydrolyze its bound GTP to GDP much more rapidly than it would without this encouragement. Thus, Ras works like a light switch that one person turns on and another turns off. You are given a mutant cell that lacks the GTPase-activating protein. What abnormalities would you expect to find in the way in which Ras activity responds to extracellular signals?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 13

A. Compare and contrast signaling by neurons, which secrete neurotransmitters at synapses, with signaling carried out by endocrine cells, which secrete hormones into the blood
B. Discuss the relative advantages of the two mechanisms.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 14

Two intracellular molecules, $X$ and $Y$, are both normally synthesized at a constant rate of 1000 molecules per second per cell. Molecule $X$ is broken down slowly: each molecule of $X$ survives on average for 100 seconds. Molecule $Y$ is broken down 10 times faster: each molecule of Y survives on average for 10 seconds.
A. Calculate how many molecules of $X$ and $Y$ the cell contains at any time.
B. If the rates of synthesis of both $X$ and $Y$ are suddenly increased tenfold to 10,000 molecules per second per cell without any change in their degradation rates- -how many molecules of $X$ and $Y$ will there be after one second?
C. Which molecule would be preferred for rapid signaling?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 15

One of the great kings of the past ruled an enormous kingdom that was more beautiful than anywhere else in the world. Every plant glistened as brilliantly as polished jade, and the softly rolling hills were as sleek as the waves of the summer sea. The wisdom of all of his decisions relied on a constant flow of information brought to him daily by messengers who told him about every detail of his kingdom so that he could take quick, appropriate actions when needed. Despite the beauty and efficiency, his people felt doomed living under his rule, for he had an adviser who had studied cell signal transduction and accordingly administered the king's Department of Information. The adviser had implemented the policy that all messengers will be immediately beheaded whenever spotted by the Royal Guard, because for rapid signaling the lifetime of messengers ought to be short. Their plea "Don't hurt me, I'm only the messenger!" was to no avail, and the people of the kingdom suffered terribly because of the rapid loss of their sons and daughters." Why is the analogy on which the king's adviser based his policies inappropriate? Briefly discuss the features that set cell signaling pathways apart from the human communication pathway described in the story.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 16

In a series of experiments, genes that code for mutant forms of an RTK are introduced into cells. The cells also express their own normal form of the receptor from their normal gene, although the mutant genes are constructed so that the mutant RTK is expressed at considerably higher concentration than the normal RTK. What would be the consequences of introducing a mutant gene that codes for an RTK (A) lacking its extracellular domain, or (B) lacking its intracellular domain?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 17

Discuss the following statement: "Membrane proteins that span the membrane many times can undergo a conformational change upon ligand binding that can be sensed on the other side of the membrane. Thus, individual protein molecules can transmit a signal across a membrane. In contrast, individual single-span membrane proteins cannot transmit a conformational change across the membrane but require oligomerization."

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 18

What are the similarities and differences between the reactions that lead to the activation of G proteins and the reactions that lead to the activation of Ras?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 19

Why do you suppose cells use $\mathrm{Ca}^{2+}$ (which is kept by $\mathrm{Ca}^{2+}$ pumps at a cytosolic concentration of $10^{-7} \mathrm{M}$ ) for intracellular signaling and not another ion such as $\mathrm{Na}^{+}$ (which is kept by the $\mathrm{Na}^{+}$ pump at a cytosolic concentration of $\left.10^{-3} \mathrm{M}\right) ?$

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 20

It seems counterintuitive that a cell, having a perfectly abundant supply of nutrients available, would commit suicide if not constantly stimulated by signals from other cells (see Figure $16-6$ ). What do you suppose might be the advantages of such regulation?

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 21

The contraction of the myosin-actin system in muscle cells is triggered by a rise in intracellular $\mathrm{Ca}^{2+}$. Muscle cells have specialized $\mathrm{Ca}^{2+}$ channels-called ryanodine receptors because of their sensitivity to the drug ryanodine- that are embedded in the membrane of the sarcoplasmic reticulum, a specialized form of the endoplasmic reticulum. In contrast to the IP $_{3}$ -gated $\mathrm{Ca}^{2+}$ channels in the endoplasmic reticulum shown in Figure $16-27$, the signaling molecule that opens ryanodine receptors is $\mathrm{Ca}^{2+}$ itself. Discuss the consequences of ryanodine channels for muscle cell contraction.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 22

Two protein kinases, $\mathrm{K} 1$ and $\mathrm{K} 2$, function sequentially in an intracellular signaling pathway. If either kinase contains a mutation that permanently inactivates its function, no response is seen in cells when an extracellular signal is received. A different mutation in $\mathrm{K} 1$ makes it permanently active, so that in cells containing that mutation a response is observed even in the absence of an extracellular signal. You characterize a double-mutant cell that contains $K 2$ with the inactivating mutation and $\mathrm{K} 1$ with the activating mutation. You observe that the response is seen even in the absence of an extracellular signal. In the normal signaling pathway, does $\mathrm{K} 1$ activate $\mathrm{K} 2$ or does $\mathrm{K} 2$ activate $\mathrm{K} 1 ?$ Explain your answer.

Charles Kirschbaum

Charles Kirschbaum

Numerade Educator

Problem 23

A. Trace the steps of a long and indirect signaling pathway from a cell-surface receptor to a change in gene expression in the nucleus.
B. Compare this pathway with two short and direct pathways from the cell surface to the nucleus.

IM

Ivonne Morales

Numerade Educator

Problem 24

How does PI 3-kinase activate the Akt kinase after activation of RTK?

Bryan Valdivia

Numerade Educator

Problem 25

Animal cells and plant cells have some very different intracellular signaling mechanisms but also share some common mechanisms. Why do you think this is so?

Bryan Valdivia

Numerade Educator