Lecture 1: Extra & Intracellular signalling and protein domains

Question 1

Name 4 classes of cell signalling

Answer 1

1. Contact dependent: requires cells to be in direct membrane– membrane contact
2. Paracrine: Paracrine signalling depends on local mediators that are released into the extracellular space and act on neighbouring cells.
3. Synaptic: performed by neurons that transmit signals electrically along their axons and release neurotransmitters at synapses, which are often located far away from the neuronal cell body.
4. Endocrine: depends on endocrine cells, which secrete hormones into the bloodstream for distribution throughout the body.

Question 2

Describe two broad classes of receptors in regards to location

Answer 2

Cell surface receptors: Most signal molecules are hydrophilic and are therefore unable to cross the target cell’s plasma membrane directly; instead, they bind to cell-surface receptors, which in turn generate signals inside the target cell.

Intracellular receptors: Some small signal molecules, by contrast, diffuse across the plasma membrane and bind to receptor proteins inside the target cell—either in the cytosol or in the nucleus. Many of these small signal molecules are hydrophobic and poorly soluble in aqueous solutions; they are therefore transported in the bloodstream and other extracellular fluids bound to carrier proteins, from which they dissociate before entering the target cell.

Question 3

How could you test for what receptor binds a given ligand?

Answer 3

Can use a radioactive ligand, inject it into the CSF. Following fixation and slicing slices can be put on radioactive film and anatomical knowledge can be used to see what receptors are there. You can also immunoprecipitate a ligand with a His tag or GFP coupled receptor.

You can then bind this with an antibody and use (agarose) beads to extract the receptor bound to the ligand. Can then use a gel assay to see radioactivity where your receptor is present.

Question 4

How would you describe the action of an antagonist in terms of specificity, affinity and effectivity

Answer 4

Antagonists can have high specificity, affinity but 0 effectivity

Question 5

How could you test for specificity?

Answer 5

Using radioactivity you could add a second receptor you think competes with it and see if the measured radioactivity at the receptor decreases

Question 6

What are meant by full agonists, partial agonists, inverse agonists and neutral agonists

Answer 6

Full agonist- Full effectivity, others unspecified; sharp rise in biological activity at certain concentration before plateau

Partial agonist- partial effectivity; more gradual rise in biological response and plateau at lower biological response

Neutral agonist- antagonist, 0 effectivity

Inverse agonist- drop in biological response; could be a constantly active receptor, binding reduces activity

Question 7

What is meant by integration in signal transduction pathways?

Answer 7

When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger X, or the membrane potential Vm, the regulatory outcome results from the integrated input from both receptor

Question 8

In responding to many types of stimuli, cells and organisms are able to detect the same percentage of change in a signal over a wide range of stimulus strengths. How do cells manage this?

Answer 8

The target cells accomplish this through a reversible process of adaptation, or desensitization, whereby a prolonged exposure to a stimulus decreases the cells’ response to that level of stimulus.

The underlying mechanism is negative feedback that operates with a short delay: a strong response modifies the signalling machinery involved, such that the machinery resets itself to become less responsive to the same level of signal

Question 9

Describe five ways in which adaptation or desensitisation could occur

Answer 9

Adaptation to a signal molecule can occur in various ways. It can result from inactivation of the receptors themselves. The binding of signal molecules to cell-surface receptors, for example, may induce the endocytosis and temporary sequestration of the receptors in endosomes. (receptor sequestration)

In some cases, such signal-induced receptor endocytosis leads to the destruction of the receptors in lysosomes, a process referred to as receptor down-regulation (in other cases, however, activated receptors continue to signal after they have been endocytosed).

Receptors can also become inactivated on the cell surface—for example, by becoming phosphorylated—with a short delay following their activation.

Adaptation can also occur at sites downstream of the receptors, either by a change in intracellular signalling proteins involved in transducing the extracellular signal or by the production of an inhibitor protein that blocks the signal transduction process.

Question 10

Describe broadly how signalling may occur for survival, growth and division, differentiation and apoptosis

Answer 10

A cell may require a given set of signals (A,B,C) in order to survive. The addition of other signals (D,E) may incur growth and division while other signals instead (F,G) may incur differentiation. The absence of these initial signals may incur cell death.

Question 11

Describe in broad terms a prototypic signal transduction pathway

Answer 11

An extracellular signal molecule may bind to a receptor protein at the plasma membrane. This may activate an intracellular signalling protein which activates another, which activates another in a cascade. This last protein may act on effector proteins which induce changes in the cell.

Question 12

Name and describe three types of effector proteins

Answer 12

Metabolic enzyme: alters the metabolism

Gene regulatory protein: Altered gene expression

Cytoskeletal protein: altered cell shape or movement

Question 13

Name the three major classes of receptors

Answer 13

Ion-channel-coupled receptors
G-protein-coupled receptors
Enzyme-coupled receptors

Question 14

Where do you find ion-channel-coupled receptors?

Answer 14

They are involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells

Question 15

What are ion-channel-coupled receptors mediated by?

Answer 15

This type of signaling is mediated by a small number of neurotransmitters that transiently open or close an ion channel formed by the protein to which they bind, briefly changing the ion permeability of the plasma membrane and thereby changing the excitability of the postsynaptic target cell.

Question 16

How do G-protein coupled receptors act?

Answer 16

G-protein-coupled receptors act by indirectly regulating the activity of a separate plasma-membrane-bound target protein, which is generally either an enzyme or an ion channel. A trimeric GTP-binding protein (G protein) mediates the interaction between the activated receptor and this target protein.

Question 17

What can happen upon the activation of the target protein via G-protein coupled receptors?

Answer 17

The activation of the target protein can change the concentration of one or more small intracellular signaling molecules (if the target protein is an enzyme), or it can change the ion permeability of the plasma membrane (if the target pro- tein is an ion channel). The small intracellular signaling molecules act in turn to alter the behavior of yet other signaling proteins in the cell.

Question 18

How are enzyme coupled receptors defined?

Answer 18

Enzyme-coupled receptors either function as enzymes or associate directly with enzymes that they activate

Question 19

What is the typical structure of an enzyme-coupled receptor?

Answer 19

They are usually single-pass transmembrane proteins that have their ligand-binding site outside the cell and their catalytic or enzyme-binding site inside.

Question 20

How varied are enzyme-coupled receptors?

Answer 20

Enzyme-coupled receptors are heterogeneous in structure compared with the other two classes; the great majority, however, are either protein kinases or associate with protein kinases, which phosphorylate specific sets of proteins in the target cell when activated.

Question 21

What are meant by ‘second messengers’? What is their function?

Answer 21

Numerous intracellular signaling molecules relay signals received by cell-surface receptors into the cell interior. The resulting chain of intracellular signalling events ultimately alters effector proteins that are responsible for modifying the behaviour of the cell. Some intracellular signalling molecules are small chemicals, which are often called second messengers (the “first messengers” being the extracellular signals). They are generated in large amounts in response to receptor activation and diffuse away from their source, spreading the signal to other parts of the cell.

Question 22

Are these second messengers water or lipid soluble?

Answer 22

Some, such as cyclic AMP and Ca2+, are water-soluble and diffuse in the cytosol, while others, such as diacylglycerol, are lipid-soluble and diffuse in the plane of the plasma membrane.

Question 23

What does it mean to say that these are like molecular switches?

Answer 23

Most intracellular signaling molecules are proteins, which help relay the signal into the cell by either generating second messengers or activating the next signaling or effector protein in the pathway. Many of these proteins behave like molecular switches. When they receive a signal, they switch from an inactive to an active state, until another process switches them off, returning them to their inac- tive state.

Question 24

The largest class of molecular switches consists of proteins that are activated or inactivated by what process? What typically carries out these processes?

Answer 24

The largest class of molecular switches consists of proteins that are activated or inactivated by phosphorylation. For these proteins, the switch is thrown in one direction by a protein kinase, which covalently adds one or more phosphate groups to specific amino acids on the signalling protein, and in the other direction by a protein phosphatase, which removes the phosphate groups

Question 25

What does the activity of any protein regulated by phosphorylation therefore depend on?

Answer 25

The activity of any protein regulated by phosphorylation depends on the balance between the activities of the kinases that phosphorylate it and of the phosphatases that dephosphorylate it. About 30–50% of human proteins contain covalently attached phosphate, and the human genome encodes about 520 protein kinases and about 150 protein phosphatases.

Question 26

What are the two main types of proetin kinases?

Answer 26

The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Others are tyrosine kinases, which phosphorylate proteins on tyrosines. The two types of protein kinase are closely related members of a large family, differing primarily in the structure of their protein substrate binding sites.

Question 27

What is meant by a kinase cascade?

Answer 27

Many intracellular signaling proteins controlled by phosphorylation are themselves protein kinases, and these are often organised into kinase cascades. In such a cascade, one protein kinase, activated by phosphorylation, phosphorylates the next protein kinase in the sequence, and so on, relaying the signal onward and, in some cases, amplifying it or spreading it to other signaling pathways.

Question 28

What is another important class of molecular switch?

Answer 28

The other important class of molecular switches consists of GTP-binding proteins. These proteins switch between an “on” (actively signaling) state when GTP is bound and an “off” state when GDP is bound. In the “on” state, they usually have intrinsic GTPase activity and shut themselves off by hydrolyzing their bound GTP to GDP

Question 29

What are the two main types of GTP-binding proteins?

Answer 29

There are two major types of GTP-binding proteins. Large, trimeric GTP-binding proteins (also called G proteins) help relay signals from G-protein-coupled receptors that activate them. Small monomeric GTPases (also called monomeric GTP-binding proteins) help relay signals from many classes of cell-surface receptors.

Question 30

What controls these GTP-binding proteins? (2)

Answer 30

Specific regulatory proteins control both types of GTP-binding proteins. GTPase-activating proteins (GAPs) drive the proteins into an “off” state by increasing the rate of hydrolysis of bound GTP.

Conversely, guanine nucleotide exchange factors (GEFs) activate GTP-binding proteins by promoting the release of bound GDP, which allows a new GTP to bind. In the case of trimeric G proteins, the activated receptor serves as the GEF.

Question 31

Do all molecular switches in signaling systems depend on phosphorylation or GTP binding?

Answer 31

No, some signaling proteins are switched on or off by the binding of another signaling protein or a second messenger such as cyclic AMP or Ca2+, or by covalent modifications other than phosphorylation or dephos- phorylation, such as ubiquitylation

Question 32

For simplicity, we often portray a signaling pathway as a series of activation steps. What additional components are important to consider? (2)

Answer 32

It is important to note, however, that most signaling path- ways contain inhibitory steps, and a sequence of two inhibitory steps can have the same effect as one activating step. This double-negative activation is very common in signalling systems

Ideally, an activated intracellular signaling molecule should interact only with the appropriate downstream targets, and, likewise, the targets should only be activated by the appropriate upstream signal. In reality, however, intracellular signalling molecules share the cytoplasm with a crowd of closely related signalling molecules that control a diverse array of cellular processes. It is inevitable that an occasional signaling molecule will bind or modify the wrong partner, potentially creating unwanted cross-talk and interference between signalling systems.

Question 33

How does a signal remain strong, precise, and specific under these noisy conditions? (2)

Answer 33

The first line of defense comes from the high affinity and specificity of the interactions between signaling molecules and their correct partners compared to the relatively low affinity of the interactions between inappropriate partners.

Another important way that cells avoid responses to unwanted background signals depends on the ability of many downstream target proteins to simply ignore such signals. These proteins respond only when the upstream signal reaches a high concentration or activity level.

Furthermore, constitutively active protein phosphatases will further reduce the impact of background phosphorylation by rapidly removing much of it. In these and other ways, intracellular signaling systems filter out noise, generating little or no response to low levels of stimuli.

Question 34

What else can contribute to this noisy system?

Answer 34

Cells in a population often exhibit random variation in the concentration or activity of their intracellular signaling molecules. Similarly, individual molecules in a large population of molecules vary in their activity or interactions with other molecules. This signal variability introduces another form of noise that can interfere with the precision and efficiency of signaling.

Question 35

How robust are signalling systems to this variation of concentration and activity?

Answer 35

Most signaling systems, how- ever, are built to generate remarkably robust and precise responses even when upstream signals are variable or even when some components of the system are disabled. In many cases, this robustness depends on the presence of backup mechanisms: for example, a signal might employ two parallel pathways to activate a single common downstream target protein, allowing the response to occur even if one pathway is crippled.

Question 36

Describe how a given signalling molecule may have a high affinity for a specific target protein

Answer 36

Protein kinases, for example, contain active sites that recognize a specific amino acid sequence around the phosphorylation site on the correct target protein, and they often contain additional docking sites that promote a specific, high-affinity interaction with the target. These and related mechanisms help provide a strong and persistent interaction between the correct partners, reducing the likelihood of inappropriate interactions with other proteins.

Question 37

Describe a strategy the cell employs to enhance the specificity of interactions between signalling molecules, possibly utilising a specific type of protein

Answer 37

One simple and effective strategy for enhancing the specificity of interactions between signaling molecules is to localise them in the same part of the cell or even within large protein complexes, thereby ensuring that they interact only with each other and not with inappropriate partners. Such mechanisms often involve scaffold proteins, which bring together groups of interacting signalling proteins into signalling complexes, often before a signal has been received

Question 38

In other cases, when this complex is not formed prior to the signal how can two similar strategies be employed?

Answer 38

In other cases, such signaling complexes form only transiently in response to an extracellular signal and rapidly disassemble when the signal is gone. They often assemble around a receptor after an extracellular signal molecule has activated it. In many of these cases, the cytoplasmic tail of the activated receptor is phosphorylated during the activation process, and the phosphorylated amino acids then serve as docking sites for the assembly of other signalling proteins

In yet other cases, receptor activation leads to the production of modified phospholipid molecules (called phosphoinositides) in the adjacent plasma membrane, which then recruit specific intracellular signaling proteins to this region of membrane, where they are activated

Question 39

What name is used to describe these methods of bringing interacting proteins together?

Answer 39

induced proximity: Simply bringing intracellular signaling proteins together into close proximity is sometimes sufficient to activate them. Thus, induced proximity, where a signal triggers assembly of a signaling complex, is commonly used to relay signals from protein to protein along a signaling pathway.

Question 40

What does the assembly of such signaling complexes depend on?

Answer 40

The assembly of such signaling complexes depends on various highly conserved, small interaction domains, which are found in many intracellular signaling proteins. Each of these compact protein modules binds to a particular structural motif in another protein or lipid

Question 41

What may this interaction domain consist of?

Answer 41

The recognised motif in the interacting protein can be a short peptide sequence, a covalent modification (such as a phosphorylated amino acid), or another protein domain.

Question 42

How may the addition of these interaction domains have facilitated the evolution of new signalling pathways?

Answer 42

because it can be inserted at many locations in a protein without disturbing the protein’s folding or function, a new interaction domain added to an existing signaling protein could connect the protein to additional signaling pathways.

Question 43

Describe four of these interaction domains in signalling pathways

Answer 43

Src homology 2 (SH2) domains and phosphotyrosine-binding (PTB) domains, for example, bind to phosphorylated tyrosines in a particular peptide sequence on activated receptors or intracellular signaling proteins.

Src homology 3 (SH3) domains bind to short, proline-rich amino acid sequences.

Some pleckstrin homology (PH) domains bind to the charged head groups of specific phosphoinositides that are produced in the plasma membrane in response to an extracellular signal; they enable the protein they are part of to dock on the membrane and interact with other similarly recruited signaling proteins

Question 44

What is meant by adaptors in signalling cascades?

Answer 44

Some signaling proteins consist solely of two or more interaction domains and function only as adaptors to link two other proteins together in a signalling pathway.

Question 45

Describe the interaction domains in the case of RTKs

Answer 45

First, the activated receptor phosphorylates itself on tyrosines, and one of the phosphotyrosines then recruits a docking protein called insulin receptor substrate-1 (IRS1) via a PTB domain of IRS1; the PH domain of IRS1 also binds to specific phosphoinositides on the inner surface of the plasma membrane.

Then, the activated receptor phosphorylates IRS1 on tyrosines, and one of these phosphotyrosines binds the SH2 domain of the adaptor protein Grb2.

Next, Grb2 uses one of its two SH3 domains to bind to a proline-rich region of a protein called Sos, which relays the signal downstream by acting as a GEF to activate a monomeric GTPase called Ras. Sos also binds to phosphoinositides in the plasma membrane via its PH domain.

Grb2 uses its other SH3 domain to bind to a proline-rich sequence in a scaffold protein. The scaffold protein binds several other signaling proteins, and the other phosphorylated tyrosines on IRS1 recruit additional signaling proteins that have SH2 domains

Question 46

Describe another way of bringing receptors and intracellular signalling molecules together

Answer 46

Another way of bringing receptors and intracellular signaling proteins together is to concentrate them in a specific region of the cell. An important example is the primary cilium that projects like an antenna from the surface of most vertebrate cells It is usually short and nonmotile and has micro- tubules in its core, and a number of surface receptors and signaling proteins are concentrated there. (Relevant to light and smell receptors)

Question 47

Name 7 ways in which the relationship between a signal and response can vary in different signalling pathways

Answer 47

1. Response timing
2. Sensitivity
3. Dynamic range
4. Persistence
5. Signal processing
6. Integration
7. Coordination

Question 48

How can the relationship between a signal and response can vary in different signalling pathways in regards to response timing?

Answer 48

Response timing varies dramatically in different signaling systems, according to the speed required for the response. In some cases, such as synaptic signaling, the response can occur within milliseconds. In other cases, as in the control of cell fate by morphogens during development, a full response can require hours or days.

Question 49

How can the relationship between a signal and response can vary in different signalling pathways in regards to sensitivity?

Answer 49

Hormones tend to act at very low concentrations on their distant target cells, which are therefore highly sensitive to low concentrations of signal. Neurotransmitters, on the other hand, operate at much higher concentrations at a synapse, reducing the need for high sensitivity in postsynaptic receptors.

Question 50

How can sensitivity be controlled in a system?

Answer 50

Sensitivity is often controlled by changes in the number or affinity of the receptors on the target cell. A particularly important mechanism for increasing the sensitivity of a signalling system is signal amplification, whereby a small number of activated cell-surface receptors evoke a large intracellular response either by producing large amounts of a second messenger or by activating many copies of a downstream signalling protein.

Question 51

What is meant by dynamic range varying the relationship between signal and response?

Answer 51

Dynamic range of a signalling system is related to its sensitivity. Some systems, like those involved in simple developmental decisions, are responsive over a narrow range of extracellular signal concentrations. Other systems, like those controlling vision or the metabolic response to some hormones, are highly responsive over a much broader range of signal strengths.

Question 52

How is broad dynamic range often achieved?

Answer 52

We will see that broad dynamic range is often achieved by adaptation mechanisms that adjust the responsiveness of the system according to the prevailing amount of signal.

Question 53

How can persistence vary in signalling systems?

Answer 53

A transient response of less than a second is appropriate in some synaptic responses, for example, while a prolonged or even permanent response is required in cell fate decisions during development. Numerous mechanisms, including positive feedback, can be used to alter the duration and reversibility of a response.

Question 54

How can the relationship between a signal and response can vary in different signalling pathways in regards to signal processing?

Answer 54

Signal processing can convert a simple signal into a complex response. In many systems, for example, a gradual increase in an extracellular signal is converted into an abrupt, switchlike response. In other cases, a simple input signal is converted into an oscillatory response, produced by a repeating series of transient intracellular signals.

Question 55

What usually lies at the heart of biochemical switches and feedback responses?

Answer 55

Feedback usually lies at the heart of biochemical switches and oscillators.

Question 56

How can the relationship between a signal and response can vary in different signalling pathways in regards to integration?

Answer 56

Integration allows a response to be governed by multiple inputs. For example, specific combinations of extracellular signals are generally required to stimulate complex cell behaviors such as cell survival and proliferation. The cell therefore has to integrate information coming from multiple signals, which often depends on intracellular coincidence detectors; these proteins are equivalent to AND gates in the microprocessor of a computer, in that they are only activated if they receive multiple converging signals

Question 57

How can the relationship between a signal and response can vary in different signalling pathways in regards to coordination?

Answer 57

Coordination of multiple responses in one cell can be achieved by a single extracellular signal. Some extracellular signal molecules, for example, stimulate a cell to both grow and divide. This coordination generally depends on mechanisms for distributing a signal to multiple effectors, by creating branches in the signaling pathway

Question 58

What does the speed of a response depend on?

Answer 58

The speed of any signalling response depends on the nature of the intracellular signalling molecules that carry out the target cell’s response.

When the response requires only changes in proteins already present in the cell, it can occur very rapidly: an allosteric change in a neurotransmitter-gated ion channel. When the response involves changes in gene expression and the synthesis of new proteins, however, it usually requires many minutes or hours, regardless of the mode of signal delivery.

Question 59

It is natural to think of intracellular signaling systems in terms of the changes produced when an extracellular signal is delivered. But it is just as important to consider what happens when the signal is withdrawn. Elaborate on this.

Answer 59

During development, transient extracellular signals often produce lasting effects: they can trigger a change in the cell’s development that persists indefinitely through cell memory mechanisms.

In most cases in adult tissues, however, the response fades when a signal ceases. Often the effect is transient because the signal exerts its effects by altering the concentrations of intracellular molecules that are short-lived (unstable), undergoing continual turnover. Thus, once the extracellular signal is gone, the degradation of the old molecules quickly wipes out all traces of the signal’s action. It follows that the speed with which a cell responds to signal removal depends on the rate of destruction, or turnover, of the intracellular molecules that the signal affects.

Question 60

Does the turnover rate affect the speed of a response?

Answer 60

Yes, after a molecule’s synthesis rate has been either increased or decreased abruptly, the time required for the molecule to shift halfway from its old to its new equilibrium concentration is equal to its half-life—that is, equal to the time that would be required for its concentration to fall by half if all synthesis were stopped

Question 61

How could you test for receptor sequestration?

Answer 61

Often the receptor is broken down following activation. Can label your ligand, should disapear from the membrane. If you have good resolution you might see it in your cell. Can then lisate your cells and see if the radioactivity is there.

Question 62

How could you test for receptor down-regulation?

Answer 62

To make the distinction between endosomes and lysosomes can use different stains for early/ late endosome and lysosomes. Can be bought or made in the lab. Can look on Thermofisher for these kits. Would see the overlap between the flourophore and GFP

Question 63

What does the term ‘relay’ mean in signal transduction?

Answer 63

To send the signal down in the same basic form

Question 64

What does it mean to transduce and amplify?

Answer 64

One signal converts and amplifies many downstream targets

Question 65

What is meant by the term spread?

Answer 65

When a downstream target sends signals to other proteins

Question 66

What does it mean to anchor?

Answer 66

Restricts signals to a certain part of the cell for a localised signalling event

Question 67

Describe how positive feedback may occur

Answer 67

A signalling ligand may bind to an inactive enzyme to make it active. The enzyme substrate may then produce a product which when bound together with the enzyme make it very active.

Question 68

What borad effect does phosphorylation have on a target?

Answer 68

Makes it more negative through conformational change (post translational modification)

Question 69

Compare signalling by phosphorylation and signalling by GTP binding

Answer 69

(A) A protein kinase covalently adds a phosphate from ATP to the signaling protein, and a protein phosphatase removes the phosphate. Many signaling proteins are activated by dephosphorylation rather than by phosphorylation.

(B) A GTP- binding protein is induced to exchange its bound GDP for GTP, which activates the protein; the protein then inactivates itself by hydrolysing its bound GTP to GDP (loses a phosphate).

Question 70

What is SH2 important for and how does it demonstrate some redundancy in protein binding domains?

Answer 70

SH2 important for phosphorylated tyrosine kinases, binds once receptor tyrosine kinases (RTKs) are phosphorylated. PTB is similar to SH2, there is some redundency

Question 71

What does PH bind?

Answer 71

PH binds phospholipids, PI3K phosphorylates lipids on the inside of the membrane. PK3/AKT also have a PH domain that can bind to these phosphorylated lipids

Question 72

Describe how positive and negative feedback can occur through protein kinases

Answer 72

In each case, the input signal is an activated protein kinase (S) that phosphorylates and thereby activates another protein kinase (E); a protein phosphatase (I) dephosphorylates and inactivates the activated E kinase.

In a positive feedback loop the activated E kinase acts back to promote its own phosphorylation and activation; the basal activity of the I phosphatase dephosphorylates activated E at a steady, low rate.

In a negative feedback loop, the activated E kinase phosphorylates and activates the I phosphatase, thereby increasing the rate at which the phosphatase dephosphorylates and inactivates the phosphorylated E kinase.

Question 73

What effect does the positive feedback have on the activity of the kinase over time?

Answer 73

Without feedback, the activity of the E kinase is simply proportional (with a short lag) to the level of stimulation by the S kinase. With the positive feedback loop, the transient stimulation by S kinase switches the system from an “off” state to an “on” state, which then persists after the stimulus has been removed.

Question 74

What effect does the negative feedback have on the activity of the kinase over time? What effect might a delay have?

Answer 74

Without feedback, the activity of the E kinase is simply proportional (with a short lag) to the level of stimulation by the S kinase.With a short delay, the system shows a strong, brief response when the signal is abruptly changed, and the feedback then drives the response back down to a lower level. With a long delay, the feedback produces sustained oscillations for as long as the stimulus is present.