Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

Question 1

The binding of a specific signaling molecule to a receptor in the plasma membrane triggers the first step in the signal transduction pathway—

Answer 1

the chain of molecular interactions that leads to a particular response within the cell.

Question 2

the signal-activated receptor activates another molecule, which activates yet another molecule, and so on, until the protein that produces the

Answer 2

final cellular response is activated.

Question 3

The molecules that relay a signal from receptor to response, which we call relay molecules in this book, are often

Answer 3

proteins.

Question 4

Keep in mind that the original signaling molecule is not physically passed along a signaling pathway; in most cases, it never even

Answer 4

enters the cell.

Question 5

At each step, the signal is transduced into a different form, commonly a

Answer 5

shape change in the next protein.

Question 6

Very often, the shape change is brought about by

Answer 6

phosphorylation.

Question 7

. An enzyme that transfers phosphate groups from ATP to a protein is generally known as a

Answer 7

protein kinase

Question 8

Recall that a receptor tyrosine kinase is a specific kind of protein kinase that phosphorylates tyrosines on the other receptor tyrosine kinase in a

Answer 8

dimer.

Question 9

Most cytoplasmic protein kinases, however, act on proteins different from

Answer 9

themselves.

Question 10

Another distinction is that most cytoplasmic protein kinases phosphorylate either of two other

Answer 10

amino acids, serine or threonine, rather than tyrosine.

Question 11

Serine/threonine kinases are widely involved in signaling pathways in

Answer 11

animals, plants, and fungi.

Question 12

Many of the relay molecules in signal transduction pathways are

Answer 12

protein kinases, and they often act on other protein kinases in the pathway

Question 13

The sequence of steps shown in the figure is similar to many known pathways, including those triggered in yeast by mating factors and in animal cells by many growth factors.

Answer 13

phosphorylation cascade

Question 14

The signal is transmitted by a cascade of protein phosphorylations, each causing a

Answer 14

shape change in the phosphorylated protein.

Question 15

The shape change results from the interaction of the newly added phosphate groups with

Answer 15

charged or polar amino acids on the protein being phosphorylated

Question 16

The shape change in turn alters the function of the

Answer 16

protein, most often activating it

Question 17

In some cases, though, phosphorylation instead

Answer 17

decreases the activity of the protein.

Question 18

About 2% of our own genes are thought to code for

Answer 18

protein kinases, a significant percentage.

Question 19

A single cell may have hundreds of different kinds, each specific for a different

Answer 19

substrate protein.

Question 20

Together, protein kinases probably regulate the activity of a

Answer 20

large proportion of the thousands of proteins in a cell.

Question 21

Among these are most of the proteins that, in turn,

Answer 21

regulate cell division.

Question 22

Abnormal activity of such a kinase can cause

Answer 22

abnormal cell division and contribute to the development of cancer.

Question 23

Equally important in the phosphorylation cascade are the _____________________, enzymes that can rapidly remove phosphate groups from proteins, a process called

Answer 23

protein phosphatases, dephosphorylation

Question 24

By dephosphorylating and thus inactivating protein kinases, phosphatases provide the mechanism for

Answer 24

turning off the signal transduction pathway when the initial signal is no longer present.

Question 25

Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to an

Answer 25

extracellular signal.

Question 26

The phosphorylation-dephosphorylation system acts as a molecular switch in the cell, turning activities

Answer 26

on or off, or up or down, as required.

Question 27

At any given moment, the activity of a protein regulated by phosphorylation depends on the

Answer 27

balance in the cell between active kinase molecules and active phosphatase molecules.

Question 28

Not all components of signal transduction pathways are

Answer 28

proteins.

Question 29

Many signaling pathways also involve small, nonprotein, water-soluble molecules or ions called

Answer 29

second messengers

Question 30

The pathway’s “first messenger” is considered to be the

Answer 30

extracellular signaling molecule—the ligand—that binds to the membrane receptor

Question 31

Because second messengers are

Answer 31

small and also water-soluble, they can readily spread throughout the cell by diffusion.

Question 32

For example, as we’ll see shortly, a second messenger called ___________ carries the signal initiated by epinephrine from the plasma membrane of a liver or muscle cell into the cell’s interior, where the signal eventually brings about glycogen breakdown.

Answer 32

cyclic AMP

Question 33

Second messengers participate in pathways that are initiated by both

Answer 33

G protein-coupled receptors and receptor tyrosine kinases.

Question 34

The two most widely used second messengers are

Answer 34

cyclic AMP and calcium ions, Ca2+ .

Question 35

A large variety of relay proteins are sensitive to

Answer 35

changes in the cytosolic concentration of one or the other of these second messengers.

Question 36

Earl Sutherland established that,

Answer 36

without passing through the plasma membrane, epinephrine somehow causes glycogen breakdown within cells.

Question 37

This discovery prompted him to search for a

Answer 37

second messenger that transmits the signal from the plasma membrane to the metabolic machinery in the cytoplasm.

Question 38

Sutherland found that the binding of epinephrine to the plasma membrane of a liver cell elevates the cytosolic concentration of

Answer 38

cyclic AMP (cAMP; cyclic adenosine monophosphate)

Question 39

an enzyme embedded in the plasma membrane, __________________________________, converts ATP to cAMP in response to an extracellular signal—in this case, provided by epinephrine.

Answer 39

adenylyl cyclase (also known as adenylate cyclase)

Question 40

But epinephrine doesn’t stimulate

Answer 40

adenylyl cyclase directly.

Question 41

When epinephrine outside the cell binds to a G protein-coupled receptor, the protein activates adenylyl cyclase, which in turn can catalyze the

Answer 41

synthesis of many molecules of cAMP.

Question 42

In this way, the normal cellular concentration of cAMP can be boosted

Answer 42

20-fold in a matter of seconds.

Question 43

The cAMP broadcasts the signal to the

Answer 43

cytoplasm.

Question 44

It does not persist for long in the absence of the hormone because a different enzyme,

Answer 44

called phosphodiesterase, converts cAMP to AMP.

Question 45

Another surge of epinephrine is needed to boost the

Answer 45

cytosolic concentration of cAMP again.

Question 46

Subsequent research has revealed that epinephrine and many other signaling molecules lead to activation of

Answer 46

adenylyl cyclase by G proteins and formation of cAMP

Question 47

The immediate effect of an elevation in cAMP levels is usually the activation of a serine/threonine kinase called

Answer 47

protein kinase A.

Question 48

The activated protein kinase A then phosphorylates various other proteins, depending on the

Answer 48

cell type.

Question 49

Further regulation of cell metabolism is provided by other G protein systems that inhibit

Answer 49

adenylyl cyclase

Question 50

In these systems, a different signaling molecule activates a different receptor, which in turn activates an inhibitory

Answer 50

G protein that blocks activation of adenylyl cyclase.

Question 51

People acquire the cholera bacterium, ______________ by drinking contaminated water.

Answer 51

Vibrio cholerae,

Question 52

The bacteria form a biofilm on the lining of the

Answer 52

small intestine and produce a toxin

Question 53

The cholera toxin is an enzyme that chemically modifies a

Answer 53

G protein involved in regulating salt and water secretion.

Question 54

Because the modified G protein is unable to hydrolyze GTP to GDP, it remains stuck in its active form, continuously stimulating

Answer 54

adenylyl cyclase to make cAMP

Question 55

The resulting high concentration of cAMP causes the intestinal cells to secrete large amounts of

Answer 55

salts into the intestines, with water following by osmosis.

Question 56

An infected person quickly develops

Answer 56

profuse diarrhea and if left untreated can soon die from the loss of water and salts.

Question 57

In one pathway, a molecule similar to cAMP called _________________ is produced by a muscle cell in response to the gas nitric oxide (NO) after it is released by a neighboring cell.

Answer 57

cyclic GMP (cGMP)

Question 58

cGMP then acts as a second messenger that causes

Answer 58

relaxation of muscles, such as those in the walls of arteries

Question 59

A compound that inhibits the hydrolysis of cGMP to GMP, thus prolonging the signal, was originally prescribed for chest pains because it

Answer 59

relaxed blood vessels and increased blood flow to the heart muscle.

Question 60

Under the trade name___________ this compound is now widely used as a treatment for erectile dysfunction in human males.

Answer 60

Viagra,

Question 61

Many of the signaling molecules that function in animals—including neurotransmitters, growth factors, and some hormones—induce responses in their target cells via

Answer 61

signal transduction pathways that increase the cytosolic concentration of calcium ions (Ca2+)

Question 62

is even more widely used than cAMP as a second messenger.

Answer 62

Calcium

Question 63

Increasing the cytosolic concentration of Ca2+ causes many responses in animal cells, including

Answer 63

muscle cell contraction, exocytosis of molecules (secretion), and cell division.

Question 64

In plant cells, a wide range of hormonal and environmental stimuli can cause brief increases in cytosolic Ca2+ concentration, triggering various signaling pathways, such as the

Answer 64

pathway for greening in response to light

Question 65

Cells use Ca2+ as a second messenger in pathways triggered by both

Answer 65

G protein-coupled receptors and receptor tyrosine kinases.

Question 66

Although cells always contain some Ca2+ , this ion can function as a second messenger because its

Answer 66

concentration in the cytosol is normally much lower than the concentration outside the cell

Question 67

In fact, the level of Ca2+ in the blood and extracellular fluid of an animal is often more than

Answer 67

10,000 times higher than that in the cytosol

Question 68

Calcium ions are actively transported out of the cell and are actively imported from the cytosol into the

Answer 68

endoplasmic reticulum (and, under some conditions, into mitochondria and chloroplasts) by various protein pumps.

Question 69

As a result, the calcium concentration in the ER is usually much higher than that in the

Answer 69

cytosol.

Question 70

Because the cytosolic calcium level is low, a small change in absolute numbers of ions represents a relatively large percentage change in

Answer 70

calcium concentration.

Question 71

In response to a signal relayed by a signal transduction pathway, the cytosolic calcium level may rise, usually by a mechanism that releases

Answer 71

Ca2+ from the cell’s ER.

Question 72

These two messengers are produced by cleavage of a certain kind of phospholipid in the plasma membrane.

Answer 72

inositol trisphosphate (IP3) and diacylglycerol (DAG).

Question 73

Because IP3 acts before calcium in these pathways, calcium could be considered a

Answer 73

“third messenger.”