Question 1

There are several methods by which cells communicate and convey signals. Turning on kinases,

phosphatases, and G-proteins can send signals to all cell parts. Together, these proteins transmit

signals from the cell's outside to its inside, where they may either activate or inhibit gene

transcription.

The cell membrane may carry signals from the outside world. Signal transduction is the process

by which cell surface receptors acquire messages from the extracellular environment. Among

others, hormones, neurotransmitters, and growth factors may activate these receptors. When

activated, a receptor initiates a chain reaction that modifies gene expression and protein function

inside the cell.

Biological molecules need not enter the cell in order to function as signals. Some signalling

molecules, such as hormones, may bind to cell surface receptors and initiate internal signalling

pathways without entering the cell. Growth factors and other signalling chemicals may enter

cells and attach to intracellular receptors. This initiates signalling pathways in the cellular

environment.

Signal transduction is the process through which cells acquire information from their

environment, assess it, and respond accordingly. This might occur through signalling pathways

inside the cell or by receptors outside the cell. These signals may alter the gene expression and

protein function, altering a cell's behaviour. This may result in altered cell behaviour.

Question 2

Most chemical messengers that may penetrate the cell membrane are tiny and lipid-based (fat-

soluble). The phospholipid-dominated lipid bilayer of the cell membrane allows these substances
to pass through readily. Peptides and steroid hormones are examples of signalling molecules that

are like fat.

In contrast, chemical signals that cannot cross the cell membrane are often large, hydrophilic, or

water-soluble. These substances cannot pass through the lipid bilayer of the cell membrane. Thus

they must utilize other pathways to enter the cell. Growth factors and cytokines are examples of

giant, water-loving, signal-transmitting molecules.

G protein-coupled receptors are an additional class of non-permeable signalling molecules. Both

sides of the cell membrane have these receptors. Hydrophilic substances such as peptides, amino

acids, biogenic amines, and even light may activate them. These receptors boost intracellular

signalling pathways when activated. Additionally, the cell may alter some signalling molecules

to allow them to travel through the membrane. This may be accomplished either by receptor-

ligand complex endocytosis or by activating enzymes that can break them down into smaller

molecules that can pass through the membrane.

Question 3

The signal is enhanced when a single signalling molecule outside the cell activates a more

significant number of signalling molecules inside the cell. This is achieved by a series of

chemical interactions that increase the number of signalling molecules activated farther down the

line.

An example of signal amplification is the activation of G protein-coupled receptors,

transmembrane receptors activated by water-loving chemicals. When a signalling molecule

activates a receptor, it puts in motion events that ultimately activate a G protein. Afterward, the

G protein activates an enzyme called adenylyl cyclase that converts ATP to cAMP. This increase
in cAMP levels activates protein kinase A, which phosphorylates and activates subsequent

signalling molecules.

Another example is making multimeric receptor complexes, which involve bringing together

many receptors to increase the number of active receptors in a specific location. Consequently,

the signalling cascade functions more effectively.

Here is a simple illustration illustrating how a signal becomes stronger:

Here is where the signal amplification diagram goes.

The image depicts how a single extracellular signalling molecule (blue circle) may bind to a cell

membrane receptor (red circle), triggering a cascade of signalling molecules farther down the

line (green circle). Consequently, the cell has more active downstream signalling molecules,

thereby strengthening the initial signal.

It is essential to realize that signal amplification is not necessarily linear. Multiple signalling

pathways and molecules may interact to fine-tune the response to the signal.

Question 4a

Over a shorter path, crosstalk would occur less often than on a long journey. Crosstalk describes

how the activity of one communication pathway may initiate or terminate the activity of another.

The more steps a route has, the greater the likelihood that distinct signalling pathways will link

and influence one another.

A shorter route contains fewer steps; therefore, there are fewer opportunities for other signalling

routes to interact with and alter the function of this pathway. The route has fewer molecules and

interactions, making it less susceptible to modification by other signalling routes. Since a longer

route contains more steps, there are more opportunities for other signalling channels to modify
its function. The route has more molecules and interactions, making it more susceptible to

modification by other signalling routes.

Usually, this is the case. Regardless of this number of components, some paths may have a

feedback loop or a positive or negative regulator that might alter how the route functions.

In general, shorter routes react to a signal more quickly and directly, while more extended

pathways influence action more slowly and intricately.

Question 4 b

A longer route would give the signal more opportunities to gain strength than a shorter one.

Signal amplification is a technique that enables a single signalling molecule to activate a greater

number of signalling molecules farther down the signalling pathway. The more steps along a

path, the more likely a signal amplifies. Because there are fewer steps and components, there are

fewer opportunities for the signal to get stronger. It is because the pathway contains fewer

molecules and interactions, reducing the likelihood that the signal will become stronger.

There are more stages and components along a longer path. Therefore there are more

opportunities for signal amplification. This is due to the increased number of molecules and

interactions along the path, which increases the likelihood that the signal will become stronger.

In a G protein-coupled receptor pathway, for instance, activation of a receptor initiates a series of

actions, including activation of a G protein, activation of adenylyl cyclase, conversion of ATP to

cAMP, and activation of protein kinase A. Each of these occurrences increases the signal

strength.

Question 4c

A shorter route would transmit data faster than a longer one. The transmission speed is the time

required for a signal to go from the extracellular to the intracellular environment. A path with
fewer steps and less time between them would be shorter. On the other side, a longer path would

have more steps, resulting in greater time between them.

There are fewer stages in a shorter strategy; therefore, there is less likelihood of becoming stuck.

It is because there are fewer molecules and interactions along this route, reducing the likelihood

of the signal delaying. Signal transduction is quicker and more direct when a route has fewer

steps.

In a lengthier procedure, there are more stages, and therefore there are more opportunities for

errors. More molecules and interactions along the path increase signal delay likelihood. The

signal transduction process is more intricate and time-consuming the more steps a route has.

When determining the quality of a route, it is crucial to realize that transmission speed is not

necessarily the most critical factor to consider and that various routes may need different

transmission speeds. For instance, slower pathways may be superior for signal transduction

because they are more precise and, consequently, superior for processes such as cell division.

Additionally, specific routes have positive feedback loops in which the signalling molecules that

follow them reactivate the receptors, amplifying the signal. It occurs more often in circuits that

need a robust and prompt response, such as the immune system.

It is crucial to remember that the optimal number of component steps for a route is not

necessarily a set number. Instead, it relies on the path's objective and the required response time.

Question 5
Question 5b

Serine, threonine, and tyrosine are eukaryotes' most commonly phosphorylated amino acids. The

hydroxyl (OH) group of serine, threonine, or tyrosine is linked to phosphate. Phosphorylation of

amino acids creates phosphoproteins, which assist cells in dividing, sending signals, and

regulating gene expression.

Question 5c

A molecule's phosphorylation is reversible, meaning the phosphate group may be withdrawn

once added. The enzyme responsible for removing the phosphate group is known as a

phosphatase. Phosphatases are classified into various categories, each serving a specific chemical

or biological purpose.

question 5d

A covalent link binds the phosphate to the protein during phosphorylation. A covalent

connection is formed when two atoms share one or more electron pairs. When atoms can steadily

exchange electrons, they have a strong connection. It is significant because covalent bonds are

far more robust than other types of bonding. It indicates that the phosphate group will remain

connected to the protein until a phosphatase enzyme removes it. It indicates that phosphorylation

may be utilized to regulate protein activity.

Question e drawing

In eukaryotes, the source of the phosphate used in phosphorylation is a molecule called

adenosine triphosphate (ATP). The structure of ATP is as follows:

HH
||

O-P-O-P-O

||

H OH

The phosphate transferred during phosphorylation comes from the terminal phosphate group (the

one at the right end of the molecule) of ATP.

Question f

Phosphorylation modifies the function of a protein by altering its structure, which may influence

its function. Adding a phosphate group to a protein might increase or decrease its activity,

depending on the kind of protein and the location of the phosphorylation.

The majority of the time, phosphorylation makes a protein active by altering its structure to make

it more active. It may occur, for instance, by creating a new binding site for another protein or

altering its stability. Dephosphorylation, which removes a phosphate group, may render a protein

inert or less active.

Phosphorylation may also modify a protein's interactions with other molecules, such as

cytoskeletal proteins, which can alter its stability and rate of degradation.

In addition, it is essential to remember that the consequences of phosphorylation might vary

greatly depending on the protein and location of phosphorylation. Some proteins may include

many phosphorylation sites, each having a unique influence on the protein's function.
Enzyme activity may also be altered by phosphorylation. Phosphorylation may activate or

inactivate protein kinases, which add a phosphate group to a protein substrate.

Question 6a

False. It is typical for many signalling pathways to be active simultaneously inside a cell. It

enables signal integration and crosstalk, which may result in coordinating many cellular

activities. For example, a cell may get a signal to divide and another to differentiate. These two

signals must be coordinated for the cell to divide and differentiate at the right moment.

Furthermore, since several signalling pathways are linked and triggered by the same or

comparable stimuli, a single signal may activate many pathways.

Question 6b

B. True.

Usually, cells inside the human body that do not receive signals remain inactive. It is because the

normal state of a cell is rest, and it needs a signal or stimulus to initiate a response. Without

stimulation, the cell remains in its initial state, not actively dividing or differentiating and

consuming no energy. When a signal is received, it is transduced via various pathways, resulting

in gene expression and cellular activity modifications.

Question 6c

True.

Different cell types might react differently to the same stimulus. It is because different cells

possess distinct receptors, signalling pathways, and downstream effectors, allowing them to react

differently to the same stimulus. Insulin, for instance, causes muscle and fat cells to absorb

glucose while liver cells produce proteins. In addition, the same signal may have distinct effects

on a cell at various phases of its growth or when it is in a different physiological condition. It is

why the same hormone, for instance, might have distinct effects on various organ systems or

health and sickness.

Question 6d

D. False.

Cell surface receptors are not always broken down during receptor-mediated endocytosis.

Receptor-mediated endocytosis is the process by which specific ligand-receptor complexes are

taken into the cell from the cell surface. After being taken inside the cell, the receptors can go

back to the cell surface or be broken down in lysosomes, depending on what the cell needs and

what kind of receptors are involved. Recycling endocytosis occurs when some receptors are

taken inside the cell and sent back to the cell surface. Some receptors are taken inside the cell

and broken down. Phosphorylation of amino acids creates phosphoproteins, which assist cells in

dividing, sending signals, and regulating gene expression.

Question 6 e

E. False.

Phosphorylation does not alter the amino acid sequence of a protein. Protein phosphorylation is a

post-translational alteration that involves adding a phosphate group. Kinases perform this

function on specific amino acid residues, often serine, threonine, or tyrosine. Phosphorylation

may alter a protein's activity, stability, localization, and interactions, but it does not alter its

amino acid sequence.

Question 7
Question 8a

No, RTK will not be phosphorylated if a mutation prevents the signal molecule from dimerizing

since dimerization is required for RTK activation. The RTKs' intracellular tyrosine kinase

domains are brought into proximity by dimerization, allowing for their phosphorylation and

activation. Phosphorylation cannot take place without dimerization.

Question 8b

Suppose a mutation prevents the phosphorylation of multiple tyrosines on RTK. In that case, it is

feasible that RTK will still dimerize, but it may not be wholly activated since tyrosine

phosphorylation is a vital stage in the activation process. The RTKs' intracellular tyrosine kinase

domains are brought into proximity by dimerization, allowing for their phosphorylation and

activation. If phosphorylation of tyrosines is not possible, the kinase domains will not activate,

and the RTK will not convey the signal downstream.

Question 9a

Yes, a mutation in the receptor's kinase (RTK) component might explain the cell's failure to

respond to an extracellular signal. The kinase component of the receptor initiates the signal

transduction cascade by phosphorylating downstream proteins. The signal transduction pathway

is not activated if this receptor portion is changed. As a result, the cell becomes permanently

insensitive to the signal molecule and does not respond to external signals.

Question 9b

Yes, this may explain why the cell behaves as it does. If the transcription factor is active even

though TK2 has not phosphorylated, the signal molecule would be unable to regulate it, and the

cell would not react. It would render the cell permanently unresponsive to external signals.

Question 9c
Yes, a mutation in TK2 that causes it to always function as a kinase might explain the behaviour

of this cell. This is because TK2 is a crucial component of the signal transduction pathway

shown in Diagram 1, particularly in transmitting signals from outside the cell to the signalling

molecules that follow. If TK2 is constantly active as a kinase, it will phosphorylate downstream

signalling molecules regardless of the presence of the extracellular signal molecule. It would

prevent the cell from responding to an external signal by "locking" the route in an active state. It

would make it seem like the cell never responded to the signal molecule.

Question 9d

Yes, this may explain why the cell behaves as it does. If a mutation in the promoter of the cell

surface receptor that binds the extracellular signal blocks its expression, the receptor will not be

on the cell surface, and the cell will be incapable of receiving and responding to the signal. It

would render the signal molecule permanently insensitive, preventing signal transduction in

response to the signal.

Question 10a

A feedback loop is a process in which the output of a system affects the input of the system. It

makes the system self-regulating. In a feedback loop, the output of a system is compared to a

desired or set point value. If the output is different from the desired value, the input is changed to

bring the output back to the desired value.

A positive feedback loop is a feedback loop in which the system's output boosts or amplifies the

input. It causes the system to change quickly and become unstable. Positive feedback loops are

rare in biology but can be seen in blood clotting, childbirth, and other physiological processes.

On the other hand, a negative feedback loop is a type of feedback loop in which the output of a

system works against or dampens the input, creating a stable, self-regulating mechanism. This
kind of feedback happens more often in biological systems and helps keep homeostasis in the

body—negative feedback loops control body temperature, blood sugar, and pressure.

Question 10 b Drawing

Question 10ci

If activating the transcription factor in Diagram 1's signal transduction pathway leads to

transcription (and subsequently translation) of a protein implicated in TK2's ubiquitin-mediated

proteolysis, a negative feedback loop would occur.

When the transcription factor is activated, it produces a protein that targets TK2 for destruction.

TK2 is an essential component of the signal transduction pathway. If it were degraded, its

activity would decrease, reducing the pathway's signals. This reduction in signalling would allow

the system to return to its usual activity level, preventing the route from becoming overactive.

Negative feedback loops are self-regulating systems that keep the body balanced and stop

pathways from becoming too active. In this instance, the initial activation is nullified by

producing a protein that targets TK2 for destruction. It restores the system to its average activity

level.

Question 10 c ii

A negative feedback loop would exist if activation of the transcription factor resulted in receptor-

mediated endocytosis of the receptor for this pathway.

When the transcription factor is activated, the cell surface receptor that binds the signal from

the outside enters the cell. It is referred to as receptor-mediated endocytosis. Once the receptor

has been internalized, it can no longer bind to the extracellular signal. Therefore, endocytosis of
the receptor would reduce the cell's sensitivity to the signal and the pathway's downstream

signalling, restoring the system's activity to its average level. This reduction in signalling would

avoid over-activation of the system and preserve cell homeostasis.

Negative feedback loops are self-regulating mechanisms that assist the body in maintaining

homeostasis and avoiding the over-activation of pathways. In this case, endocytosis of the

receptor serves as a counterweight to the initial activation and restores the system's activity to its

average level.

11a

. The presence of the signal in the cell's environment suggests that the signal transduction

pathway is active, yet, the absence of the receptor and TK2 phosphorylation indicates that not all

components of the route are engaged. It might be due to various issues, such as the signal's

failure to bind to the receptor, the receptor's dysfunction, or TK2's inability to phosphorylate due

to a mutation or other issues. In addition, additional cellular pathways or regulatory mechanisms

may restrict the activation of certain route components. Additional study and analysis would be

necessary to determine the specific cause of the pathway's insufficient activation.

Question 11 b

The receptor may have been removed from the cell surface by ubiquitin-mediated proteolysis.

Ubiquitination is the process in which ubiquitin binds to a target protein. It instructs the

proteasome to degrade the specified protein. This process is known as "ubiquitin-mediated

proteolysis." Adding ubiquitin to a protein instructs the cell to degrade that protein. It may occur
at the cell surface or inside the cytoplasm. Therefore, ubiquitination removes a receptor from the

cell surface if it is a ubiquitination target.

Question 11ci

The enzyme phosphatase removes a phosphate group (PO4) from a molecule. It is the reverse of

the function of a kinase, which is to add a phosphate group. If a phosphatase were to attack TK2,

it would remove a phosphate group from TK2, reducing its activity.

Question 11cii

This would be a negative feedback loop if this phosphatase were produced or activated in

response to TFa activation.

In a feedback loop, the output of a system is utilized to control the input of the same system. In a

negative feedback loop, a rise in a system's output causes its input to decrease, restricting its

output.

In this instance, the activation of TFa would serve as the input, and phosphatase would serve as

the output. The activation of TFa would result in the creation or activation of the phosphatase,

which would reduce the activity of TK2 by removing a phosphate group. In turn, this would

reduce TFa activity, decreasing the initial surge in TFa activity.

Question 11 Civ

There are other methods in which TFa might still be phosphorylated if TK2 is dephosphorylated,

and the signal response could still occur. The presence of additional kinases that may

phosphorylate TFa is one such route. Dephosphorylating TK2 would not change how TFa is

phosphorylated because another kinase in the signalling chain may phosphorylate

it before TK2.
Another potential mechanism is feedback loops. The dephosphorylation of TK2 by phosphatase

activity may represent a negative feedback loop that controls the activity of the kinase upstream

of TK2. This would result in a decrease in TK2 activity but does not affect TFa phosphorylation.

Proteolysis and endocytosis may play a function in signalling pathway modulation. A

phosphorylated TFa receptor may be removed from the cell surface by proteolysis, but new

receptors can be produced and exposed. Endocytosis may remove and recycle cell surface

receptors, but new receptors might be surface exposed in response to a signal.

Lastly, the interaction between distinct signalling pathways may also result in TFa

phosphorylation. For instance, another signalling route may independently activate a kinase that

may phosphorylate TFa, independent of TK2.In this case, dephosphorylation of TK2 does not

affect TFa phosphorylation because a different mechanism phosphorylates TFa.

Even if TK2 is dephosphorylated, TFa might still be phosphorylated by any of these methods,

and the signal response could still occur.