Chapter 9

Question 1

What are the two general reasons for cell signaling?

Answer 1

Responding to environmental changes: changes in the environment are a persistent feature of life, and cells are continually faced with alterations in temperature and availability of nutrients, water, and light. Being able to respond to change at the cellular level is called a cellular response

cell-to-cell communication: cells share information with each other

Question 2

Compare and contrast the five ways cells communicate with each other based on the distance between them

Answer 2

Direct intercellular signaling: Signals pass through a cell junction from the cytosol of one cell to adjacent cells

Contact-dependent signaling: membrane-bound signals bind to receptors on adjacent cells

Autocrine signaling: cells release signals that affect themselves and nearby target cells. when the cell density is high, the concentration of autocrine signals is also high

Paracrine signaling: cells release signals that affect nearby target cells (close proximity); short duration - signal is broken down too quickly to be carried to other parts of the body and affect distance cells

Endocrine signaling: cells release signals that travel long distances to affect target cells (hormones)

Question 3

Outline the basic processes of cell signaling

Answer 3

Receptor activation: The binding of a signaling molecule causes a conformational change in a receptor that activates its function

Signal transduction: The activated receptor stimulates a series of proteins that forms a signal transduction pathway

Cellular response: The signal transduction pathway affects the functions and/or amounts of cellular proteins, thereby producing a cellular response

Question 4

Compare and contrast three general types of cell surface receptors

Answer 4

Enzyme-linked receptors: Many human hormones bind to this type of receptor (insulin binds to an enzyme-linked receptor in muscles cells - enhances the ability of those cells to use glucose); has two domains - an extracellular domain [binds to a signaling molecule] and intercellular domain [catalytic function]; most types of elr function as protein kinases (enzymes that transfer a phosphate group from ATP to a specific amino acid in a protein)

G-protein-coupled receptors (GPCRs): common type of receptor found in the cells of eukaryotic species that interacts with G proteins (has ability to bind GTP and GDP) to initiate a cellular response; recognize a wide range of ligands including photons, small molecules, and proteins to open or close ion channels through the activation of the intracellular messenger, G-protein

Ligand-gated ion channels: pores in the cellular membrane that allow ions to pass in and out of the cell upon binding with neurotransmitters

Question 5

Describe intracellular receptors, using estrogen receptors as an example

Answer 5

Intracellular receptors: found on inside of cell, typically in the cytoplasm or nucleus. In most cases, the ligands of intracellular receptors are small, hydrophobic (water-hating) molecules since they have to cross the plasma membrane in order to reach their receptors. These receptors cause change directly, binding to the DNA and altering transcription themselves.

Estrogen receptors: group of proteins found inside the cell. Two forms: alpha and beta. After the binding occurs, the estrogen receptor subunit undergoes a conformational change that enables it to form a dimer with another subunit that also has estrogen bound. The dimer, which is the active estrogen receptor, then binds to the DNA and activates the transcription of specific genes. The estrogen receptor is an example of a transcription factor - a protein that regulates the transcription of genes. The expression of specific genes changes cell structure and function in a way that results in a cellular response

Question 6

Describe how a cell’s response to a hormone depends on the genes it expresses

Answer 6

Hormone reception
Hormone-receptor complex formation: in the cytoplasm these hormones bind with specific receptors to form a hormone-receptor complex
Gene Activation: The complex moves into the nucleus of the cell. In nucleus, the complex binds to DNA sequence
Gene transcription and translation: binding of complex to DNA sequence (HRE hormone response element) triggers gene transcription and translation
Cell function alteration: the corresponding protein product can then mediate changes in cell function

Not all genes are turned on all the time in every cell. This is why different types of cells can respond differently to the same hormone.

Question 7

Describe the signal transduction pathway of receptor tyrosine kinases (RTKs)

Answer 7

allows cells to respond effectively to external signals, regulating various cellular functions

RTKs mediate responses to a large number of signals, including peptide hormones like insulin and growth factors like epidermal growth factor.

When a signal molecule binds to the extracellular domains of RTK molecules, it causes two receptor molecules to dimerize (come together and associate).

This brings the cytoplasmic tails of the receptors close to each other and causes the tyrosine kinase activity of these tails to be turned on.

The activated tails then phosphorylate each other on several tyrosine residues in a process called autophosphorylation.

The phosphorylation of tyrosines on the receptor tails triggers the assembly of an intracellular signaling complex on the tails.

The newly phosphorylated tyrosines serve as binding sites for signaling proteins that then pass the message on to yet other proteins.

An important protein that is subsequently activated by the signaling complexes on the RTKs is called Ras

Question 8

Describe the signal transduction pathway of G-protein coupled receptors

Answer 8

Allows cells to respond effectively to external signals, regulating various cellular functions

GPCRs respond to a wide range of external signals. When a ligand binds to a GPCR, it triggers a complex chain of events involving G-proteins and second messengers

The ligand binding causes a conformational change in the receptor, which allows it to interact with a G-protein that will then pass the signal on to other intermediates in the signaling pathway

G-proteins are composed of three subunits called alpha, beta, and gamma. The alpha subunit can bind GDP or GTP and is capable of hydrolyzing a GTP molecule bound to it into GDP

When a ligand binds, the inactive G-protein can bind to a newly-revealed site on the receptor specific for its binding. Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP

Question 9

Explain how receptor tyrosine kinase and G-protein coupled receptor pathways lead to a cellular response

Answer 9

In both pathways, when a ligand binds to the GPCR, it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein’s α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type

These pathways are crucial for transmitting signals from outside the cell to inside, leading to various cellular responses

Question 10

Relate the function of second messengers to signal transduction pathways

Answer 10

Second messengers are molecules that relay signals received at receptors on the cell surface to target molecules in the cytosol and/or nucleus. They amplify the strength of the signal and trigger physiological changes at the cellular level such as proliferation, differentiation, migration, survival, apoptosis, and depolarization. Second messengers are produced catalytically in response to extracellular signals and are a part of signal transduction cascades. In a signaling pathway, second messengers, enzymes, and activated proteins interact with specific proteins, which are in turn activated in a chain reaction that eventually leads to a change in the cell’s environment

Question 11

List examples of second messengers and explain how they exert their effects

Answer 11

Second messengers are intracellular signaling molecules that respond to primary messengers. They amplify their effects and/or turn on downstream effectors
Ex. cAMP; rise in cAMP can change the molecular activities in the cytosol or turn on a new pattern of gene transcription. A hormone that achieves its effects through cAMP as a second messenger is adrenaline

Question 12

Receptor

Answer 12

A protein molecule that binds to a specific molecule

Question 13

Signal Transduction

Answer 13

Signal transduction is the process of transferring a signal throughout an organism, especially across or through a cell. Signal transduction relies on proteins known as receptors, which wait for a chemical, physical, or electrical signal. Chemical signals are called ligands, and can be produced by organisms to control their body or received from the environment. Regardless of which type of signal, it must be transferred throughout the body and across cell membranes. This process is known as signal transduction. The chains of molecules that relay signals inside a cell are known as intracellular signal transduction pathways

Question 14

Ligand

Answer 14

A molecule that binds to another specific molecule, in the case of signal transduction, the ligand binds to the receptor on the target cell. When a ligand binds to a cell-surface receptor, the receptor’s intracellular domain changes in some way (generally takes on a new shape, which may make it active as an enzyme or let it bind other molecules) The change in the receptor sets off a series of signaling events

Question 15

Quorum sensing

Answer 15

A way for bacteria to communicate and coordinate their actions based on their population density

Question 16

Endocrine

Answer 16

A cell targets a distant cell using the circulatory system to transport ligands

Question 17

Paracrine

Answer 17

A cell targets a nearby cell

Question 18

Autocrine

Answer 18

A cell targets itself

Question 19

Juxtacrine

Answer 19

Occurs through direct contact between two cells

Question 20

Binding affinity

Answer 20

The strength of the binding interaction between a single biomolecule (DNA) to its ligand or binding partner

The strength of the ligand-receptor interaction (binding affinity) can influence the efficiency and intensity of the signal transduction. A higher binding affinity means that the ligand and receptor fit together very well, and a lower binding affinity might result in less efficient signaling

Question 21

Intracellular vs transmembrane receptor

Answer 21

Intracellular receptors are located inside the cell and respond to hydrophobic ligands that can cross the plasma membrane, while the transmembrane receptors are located on the cell surface and respond to external ligands. Both types of receptors play crucial roles in cell communication and signaling

Question 22

Ligand-gated ion channels

Answer 22

When a ligand, such as a neurotransmitter, binds to a LGIC on the cell surface, it causes the receptor to change shape. This change opens the ion channel, allowing ions to flow across the membrane. The flow of ions results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. The channels covert external signals into cellular responses

Question 23

G-protein-coupled receptor

Answer 23

G-proteins function as a switch, being turned on and off by signal-receptor interactions on the cell surface. When a G protein is active, its GTP bound alpha subunit and beta-gamma dimer can interact with other membrane proteins involved in signal transduction to relay messages throughout the cell
Two signal transductions pathways that involve these receptors: cAMP and phosphatidylinositol signal pathways

• converts external signals into cellular responses through complex signaling pathways

Question 24

Protein kinase

Answer 24

An enzyme that transfers a phosphate group from ATP to a specific amino acid in a protein.

Question 25

Transduction

Answer 25

1. Signal Reception: ligand binds to specific receptor on the cell surface, which is usually a protein specific to the signaling molecule
2. Signal Transduction: binding of the ligand causes a change in the receptor’s shape, allowing it to activate other proteins inside the cell. This sets off a chain of events where one protein activates another, which activates another, and so on (signaling cascade)
3. Response: signal reaches its target (enzyme or gene), and the target’s activity is altered in some way, leading to a change in the cell’s behavior
4. Termination: once the desired response has been achieved, the signal is terminated to prevent overactivity. This can happen through the removal of a ligand from the receptor or the deactivation of proteins in the signaling cascade

Question 26

Amplification

Answer 26

enhances the response to a signal, ensuring that the cell responds appropriately to its environment

Ex. When a ligand binds to a cell-surface receptor, it can trigger a series of signaling events. The receptor may activate another signaling molecule inside of the cell, which in turn activated its own target

Question 27

Termination

Answer 27

ensures the cell does not overreact to a signal
ex. Degrading or removing the ligand, dephosphorylation, or degradation of second messengers (cAMP)

Question 28

Secondary messenger (cAMP)

Answer 28

cAMP is a derivative of ATP and is used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway
The enzyme, adenylyl cyclase, converts ATP into cAMP. cAMP transfers the effects of hormones, like adrenaline, through the plasma membrane. It’s involved in the activation of protein kinases

Question 29

GTP

Answer 29

G-protein exchanges GDP for GTP, activating the G-protein and enabling it to transmit the original activating signal to downstream effector proteins

Question 30

What are the stages of how cells respond to signals?

Answer 30

1. Reception: cell detects a signaling molecule from the outside of a cell. A signal is detected when the chemical signal (ligand) binds to the receptor protein on the surface or inside the cell
2. Transduction: Signaling molecule binds to the receptor, changing the receptor protein in some way, which initiates the process of transduction. Each relay molecule in the signal transduction pathway changes the next molecule in the pathway
3. Response: the signal triggers a specific cellular response. The response could be changing the metabolism of the cell receiving the signal to resulting in a change in gene expression (transcription) within the nucleus of the cell, or both.

These stages allow cells to receive and respond to signals from their environment, leading to appropriate cellular responses

Question 31

Briefly explain the location of the cellular receptor and the mechanism of action of steroid hormones

Answer 31

when a steroid hormone enters a cell, it binds to its specific receptor in the cytosol, forming a receptor-hormone complex. This complex then travels into the nucleus and binds to another specific receptor on the chromatin. Once bound to it, this steroid hormone-receptor complex calls for the production of mRNA by transcription. The mRNA molecules are modified and transported to the cytoplasm. The mRNA molecules code for the production of proteins through a process called translation

Question 32

Explain the strength of binding between a ligand and a receptor

Answer 32

Binding affinity - high-affinity ligand binding results from greater attractive forces between the ligand and its receptor, while low-affinity ligand binding involves less attractive force. The ligan and receptor are closely matched pairs, with a receptor recognizing just one (or a few) specific ligands, and a ligand binding to just one (or a few) target receptors. The interaction between the receptor and ligand is typically non-covalent

Question 33

Explain different factors that allow cells to respond to signaling molecules in unique ways

Answer 33

1. Variety of Receptors
2. Variety of Ligands and Signals
3. Cellular Response
4. Cell type

Question 34

Briefly, discuss the signal transduction pathway and the proteins involving cAMP

Answer 34

cAMP signaling pathway:
1. Activation of Adenylyl Cyclase: signaling molecule binds to a G-protein-coupled receptor on the cell surface. This activates the G-protein, which then activated adenylyl cyclase
2. Production of cAMP: Adenylyl cyclase converts ATP into cAMP, a second messenger
3. Activation of protein kinase A: cAMP binds to and activates an enzyme called protein kinase A. PKA is composed of two catalytic and two regulatory subunits. Upon binding of cAMP, the catalytic subunits are released from the regulatory subunits, allowing the enzyme to carry out its function, namely phosphorylating other proteins
4. Cellular Response: PKA modulates a number of cellular substrates via phosphorylation, including transcription factors, ion channels, transporters, exchangers, intracellular calcium handling proteins, and the contractile machinery

Question 35

Briefly, discuss how G proteins can help produce second messengers

Answer 35

When a signaling molecule binds to a G protein-coupled receptor (GPCR) on the cell surface, the receptor changes shape and interacts with an inactivated G-protein complex. The complex that binds is specific to the receptor. Once coupled to the receptor, the GDP molecule is exchanged for a GTP molecule, activating the G-protein.

After activation, the G-protein complex separates into the alpha-GTP subunit and the beta-gamma subunit. Both components can alter the function of effector proteins in the cell. Effector protein functions can range from altering ion permeability across the membrane by opening ion channels to initiating second messenger cascades.

Specific targets for activated G proteins include various enzymes that produce second messengers, such as cyclic AMP (cAMP), inositol triphosphate (IP3), diacylglycerol (DAG), etc. These second messengers help to regulate a number of body functions ranging from sensation to growth to hormone release

Question 36

Distinguish between synaptic, paracrine, and endocrine mechanisms of cell signaling

Answer 36

Synaptic signaling: occurs in nerve cells. A neurotransmitter is released from the presynaptic cell and travels across a very small gap called the synaptic cleft to the postsynaptic cell

Paracrine: cells communicate over relatively short distances. The signals, or ligands, are released by a cell and act on nearby cells. Moves by diffusion through the extracellular matrix and are normally quickly degraded by enzymes or removed by neighboring cells to keep the response localized

Endocrine: involves hormones; hormones are secreted into the circulatory system and travel long distances to reach their target cells. Hormones can travel via circulation to reach their targets, which are distant from the endocrine cells

Question 37

What is the long distance chemical signaling mechanism within an animal?

Answer 37

Endocrine signaling
Endocrine cells produce hormones and secrete them into the bloodstream. Once in the bloodstream, these hormones can travel throughout the body and interact with cells that have the appropriate receptors. The interaction of a hormone with its receptor typically triggers a biological response within the target cell

Question 38

What is a secondary messenger?

Answer 38

Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules, which are the first messengers. They relay signals received at receptors on the cell surface, such as the arrival of protein hormones, growth factors, etc., to target molecules in the cytosol and/or nucleus

They also amplify the strength of the signal
cAMP (cyclic AMP) is an example of this

Question 39

Describe the structure and function of G protein-coupled receptors (GPCRs)

Answer 39

GPCRs are composed of a transmembrane region that crosses the lipid bilayer seven times. This transmembrane region is coupled with a G-protein. They have no integral enzyme activity or ion channel, therefore all their downstream effects are mediated via their G-protein

Function: When an agonist (ligand) binds to the extracellular portion of the GPCR, it causes a conformational change in the receptor, resulting in the release of GDP from the α-subunit of the G-protein. Released GDP is then replaced with a GTP. This activates the G-protein, causing the α-subunit and bound GTP to dissociate from the transmembrane portion of the GPCR and βγ-subunit. These α-subunits interact with their relevant effectors and cause downstream effects, e.g., ion channel opening or enzyme activity regulation

Question 40

Describe the events by which receptor tyrosine kinases bring about a cellular response

Answer 40

Receptor tyrosine kinases (RTKs) are cell-surface proteins that trigger key cellular responses, such as survival, proliferation, differentiation, migration, and cell-cycle control. They act as signal transducers that mediate cell-to-cell communication by phosphorylating tyrosine residues on key intracellular substrate proteins

1. Signal Binding: signaling molecule binds to extracellular domain of an RTK, which causes two receptor molecules to come together, bringing the cytoplasmic tails of the receptors close to each other
2. Activation of Tyrosine Kinase Domains: The dimerization causes the tyrosine kinase activity of these tails to be turned on. The activated tails then phosphorylate each other on several tyrosine residues in a process called autophosphorylation
3. Assembly of Signaling Complex: Phosphorylation of tyrosines on the receptor tails triggers the assembly of an intracellular signaling complex on the tails. The newly phosphorylated tyrosines serve as a binding sites for signaling proteins that then pass the message on to yet other proteins
4. Activation of Ras Protein: An important protein that is activated by the signaling complexes on the RTKs is called Ras. The Ras protein is a monomeric guanine nucleotide binding protein that is associated with the cytosolic face of the plasma membrane

Question 41

Signals that have a direct effect on cells that are in the immediate area are ________ signals.
a. Endocrine
b. Paracrine
c. Direct
d. Synaptic

Answer 41

b. Paracrine

Question 42

Phosphorylation is versatile because it is reversible due to enzymes that can remove phosphate
groups.
True or False

Answer 42

True

Phosphatases can remove phosphate groups from proteins
Kinases add phosphate groups, and phosphatases removes them. The ability to rapidly switch between these two states contributes to the control of a wide range of cellular processes, such as signal transduction

Question 43

A chemical that binds to a receptor with the channel directly on it is a(n) —
a. G protein-coupled receptor
b. Chemically gated ion channel
c. Enzymatic receptor
d. Intracellular receptor
e. All of these act in this manner

Answer 43

b. Chemically gated ion channel
They open to allow ions to pass through the membrane in response to the binding of a chemical messenger (ligand) such as a neurotransmitter. The other options represent different types of receptors that respond to chemical signals in various ways, but they do not have a channel directly on them that opens in response to ligand binding

Question 44

Because steroid hormones _________, they can bind to intracellular receptors.
a. Are hydrophilic
b. Are hydrophobic
c. Can cross the membrane
d. Are nonpolar
e. B, C and D are all true

Answer 44

e. B, C, and D are all true. Steroid hormones are hydrophobic, can cross the membrane, and are nonpolar. These properties allow them to easily pass through the cell membrane and bind to intracellular receptors

Question 45

Norepinephrine is a hormone that is released into the blood when the adrenal gland is stimulated by
the sympathetic preganglionic neurons. What type of signaling effect does this represent?
a. Endocrine
b. Paracrine
c. Synaptic
d. Direct contact

Answer 45

A. Endocrine. Norepinephrine is released into the blood by the adrenal gland, which is an endocrine gland. This represents endocrine signaling, where hormones are secreted directly into the bloodstream and can travel throughout the body to act on target cells

Question 46

______ rely on _______, such as Ca2+, cyclic GMP, and cyclic AMP, to activate (or inactivate) a variety of pathways within the cell.
a. Intracellular receptors; ligands
b. G protein-coupled receptors; secondary messengers
c. Receptor enzymes; G proteins
d. G protein-coupled receptors; G proteins

Answer 46

b. G protein-coupled receptors; secondary messengers

G protein-coupled receptors rely on secondary messengers, such as Ca2+, cyclic GMP, cAMP, to activate (or inactivate) a variety of pathways within the cell

Question 47

Synaptic signaling is a specialized from of ________signals.
a. Endocrine
b. Paracrine
c. Direct
d. Autocrine

Answer 47

b. Paracrine
Synaptic signaling is a specialized form of paracrine signaling that occurs in neurons

Question 48

Cellular responses can occur by —
a. Altering the cells metabolism
b. Altering cell shape or movement
c. Altering gene expression which can affect the proteins function or number of proteins
d. A and B are correct
e. A, B and C are correct

Answer 48

e. A, B, and C are correct
Cellular responses can indeed occur by altering the cell’s metabolism, altering cell shape or movement, and altering gene expression which can affect the protein’s function or number of proteins

Question 49

Most enzyme linked receptors that phosphorylate proteins are —
a. Ligand gates
b. G-Protein-Coupled Receptors
c. Protein kinases
d. All can phosphorylate
e. None can phosphorylate

Answer 49

c. Protein kinases

Protein kinases are a type of enzyme-linked receptor that can phosphorylate proteins. They do this by transferring a phosphate group from ATP to a specific amino acid in a protein. This process is crucial for regulating protein function and cellular processes. Ligand-gated channels and G-protein-coupled receptors are other types of cell surface receptors, but they do not directly phosphorylate proteins. They typically work by triggering intracellular signaling cascades when a ligand binds to them