Cell signalling - Week 22 & 23

Question 1

what is signaling and signal transduction meaning

Answer 1

Signaling and signal transduction are interchangeable terms that refer to the complex process by which cells communicate and respond to stimuli. It involves molecular events triggered by binding of signaling molecules to receptors, leading to cellular responses.

Question 2

what is signal transduction

Answer 2

Signal transduction is the process by which an extracellular signal, such as a hormone, neurotransmitter, or growth factor, is converted into an intracellular signal inside a cell. This conversion typically involves a cascade of molecular events, including receptor activation, intracellular signaling molecule activation, and ultimately leading to a cellular response.

Question 3

what is the pathway of cellular signal transduction sequence occur in

Answer 3

STIMULI –>SENSOR–> SIGNAL TRANSDUCTION–> RESPONSE(receptor)

1. Cells sense environmental signals via receptors.
2. Receptors trigger intracellular signal transduction pathways.
3. Signal transduction leads to cellular responses.

This simplified sequence captures the key steps of how cells detect, transmit, and respond to signals, allowing them to adapt and function in response to their environment.

Question 4

how are signal in cellular signal transduction regulated and why

Answer 4

signals in cellular signal transduction are regulated in both time and space. Cells carefully regulate the timing and location of signal transduction events to ensure precise and coordinated cellular responses.

Question 5

what does normal cell signaling play a role in

Answer 5

Normal cell signaling plays a critical role in regulating many, if not all, aspects of whole body homeostasis. Cell signaling pathways are involved in coordinating and regulating various physiological processes in the body, including metabolism, growth and development, immune responses, neuronal signaling, hormone regulation, and many others.

Question 6

what is a effector

Answer 6

a component of a signalling pathway that is activated following engagement of a receptor.

Question 7

what is signal transduction pathway meaning

Answer 7

the set of molecular events that convert one specific signal into one specific cellular response.

Question 8

what is a ligand

Answer 8

A molecule coming from a distance that binds to a receptor on the surface or inside a cell, acting as the primary messenger.

Question 9

what is a receptor

Answer 9

Proteins on the cell surface or inside the cell that bind to specific ligands and transmit the signal to the cell’s interior.

Question 10

what are second messengers

Answer 10

Intracellular signaling molecules that are produced in response to ligand-receptor binding and transmit the signal further within the cell.

Question 11

what are target genes

Answer 11

Specific genes in the cell’s DNA that are regulated by the intracellular signals and can be influenced by the second messengers.

Question 12

what are some example of ligands

Answer 12

Ligands can include a wide range of molecules that can bind to receptors and initiate cellular signal transduction. Some examples of ligands include:
* Growth factors and cytokines
* Hormones
* Cell Adhesion Molecules
* Lipids
* Neurotransmitters

Question 13

what are some examples of different types of receptors

Answer 13

some examples of different types of receptors are:
* Receptor tyrosine kinases
* G-protein-coupled receptors
* Nuclear receptors

Question 14

what are some examples of different types of transducers

Answer 14

some examples of different types of transducers are:
* Small monomeric GTPases
* Kinases

Question 15

how is mating in yeast cells carried out in 3 steps

Answer 15

Yeast sexual mating is regulated by signal transduction,
which involves a series of events that ultimately lead to:
1. the exchange of mating factors
2. mating,
3. the formation of a new a/α cell.

Question 16

how do cells communicate to each other

Answer 16

Cells have the ability to sense and respond to specific chemical signals in their environment, allowing them to communicate with each other. This communication can occur directly through cell-cell contacts or indirectly through the release of chemical signals into the extracellular environment.

Question 17

why is cells being able to communicate with each other crucial

Answer 17

In multicellular organisms, this ability to communicate and respond to signals is crucial for achieving coordinated activities among different specialized cells and tissues. It allows for the development, growth, and maintenance of the organism, as well as the regulation of homeostasis.

Question 18

what are 2 examples of cell signalling

Answer 18

There are different types of cell signaling, including:
1. Endocrine signaling: This type of signaling involves the release of chemical signals, called hormones, into the bloodstream by endocrine glands.
2. Paracrine signaling: This type of signaling involves the release of chemical signals, called local mediators, by cells that act on nearby cells within the same tissue or organ.

Question 19

what does cell signalling involve and why

Answer 19

cell signaling involves the reception, transduction, amplification, integration, and response to signals, which allows cells to communicate and respond to their environment

Question 20

what can messenger molecules be chemically charaterised by

Answer 20

Messenger molecules, also known as signaling molecules or ligands, can be chemically characterized as amino acids (or derivatives), peptides, proteins, fatty acids, nucleosides, or nucleotides

Question 21

where do hydrophilic and hydrophobic messenger molecules usually work/act

Answer 21

messenger molecules can be hydrophilic, meaning they dissolve in water, and typically act on receptors on the cell surface. Hydrophobic messengers, on the other hand, are typically not soluble in water and tend to act on receptors located in the nucleus or cytosol of the target cell.

Question 22

what is the interaction between the messenger molecule and its receptor known as

Answer 22

The interaction between the messenger molecule and its specific receptor is often likened to a “key and lock” mechanism, where the ligand (key) fits into the receptor (lock) to initiate a cellular response.

Question 23

what can steroid hormones and retinoids regulate

Answer 23

hydrophobic messengers, such as steroid hormones and retinoids can regulate gene transcription, leading to changes in gene expression and subsequent cellular responses.

Question 24

how do cell distinguish messengers from other chemicals in the environment

Answer 24

The combination of receptor specificity, ligand-receptor interactions, and the positioning of appropriate amino acid side chains in the binding site of the receptor allow cells to distinguish messengers from other chemicals in the environment and ensure high specificity in ligand-receptor interactions, allowing for precise signaling and communication within cells.

Question 25

how do ligands bind to their receptors with high specificity

Answer 25

Ligands form multiple noncovalent bonds with their binding site in the receptor

Question 26

how does ligand bind to its receptor

Answer 26

The binding of a ligand to its receptor is similar to the binding of an enzyme to its substrate. When a receptor binds its ligand, it becomes occupied.

Question 27

what is the amount of receptos that is occupied proportional to

Answer 27

The amount of receptor that is occupied by the ligand is proportional to the concentration of free ligand in solution. As the ligand concentration increases, more receptors become occupied until most of them are occupied, reaching saturation.

Question 28

what are growth factors and cytokines, where are they involved, with example

Answer 28

Peptides/small proteins secreted from cells, involved in paracrine and autocrine signalling. e.g. Epidermal Growth Factor (EGF)

Question 29

what are hormones, where are they involved, with example

Answer 29

Peptides, amino acids or small molecules (e.g. steroids) involved in endocrine signalling. e.g. Testosterone

Question 30

what are cell adhesion molecules involved in, with examples

Answer 30

Cell Adhesion Molecules are Involved in direct interaction between cells e.g. Cadherins, or interaction between cells and the extracellular matrix e.g. Integrins

Question 31

what are lipids, where are they involved, with example

Answer 31

Hydrophobic signalling molecules involved in autocrine and paracrine signalling e.g. prostaglandin

Question 32

what are neutransmitters, what do they, with example

Answer 32

Small hydrophilic molecules, often derived from amino acidsor nucleotides. Transmit signals across a synapse e.g. dopamine

Question 33

How do GPCRs and Kinase Coupled Receptors transmit signals upon ligand binding, and what are the downstream signaling pathways they activate

Answer 33

Plasma membrane receptors are diverse and can be classified as G-Protein Coupled Receptors (GPCRs) or Kinase Coupled Receptors. Upon ligand binding, GPCRs activate intracellular G-proteins, while Kinase Coupled Receptors activate kinase activity.

Question 34

why do downstream signaling pathways of GPCRs and Kinase Coupled Receptors diverge/converge

Answer 34

Downstream signaling pathways can diverge or converge which allows cells to integrate and process multiple signals for precise cellular responses. These signaling events play critical roles in cell function and development.

Question 35

How do RTKs transmit signals upon ligand binding and the role of tyrosine phosphorylation in this process

Answer 35

Enzyme-linked receptors, like Receptor Tyrosine Kinases (RTKs), undergo conformational changes and dimerization upon ligand binding, activating their intrinsic kinase activity. This results in phosphorylation of tyrosine residues, which serve as binding sites for other proteins.

Question 36

what do G-proteins play a role in, and what happens upon ligand binding

Answer 36

G-protein-coupled receptors (GPCRs) are plasma membrane receptors that play a crucial role in cellular signaling. Upon ligand binding, GPCRs activate intracellular G-proteins, triggering downstream signaling responses.

Question 37

where are intracellular receptors located

Answer 37

Intracellular receptors, like androgen receptor (AR), are located inside the cell.

Question 38

what does ligand binding trigger

Answer 38

Ligand binding, such as testosterone, triggers receptor activation and translocation to the nucleus.

Question 39

what complications can occur in ligand-receptor interaction

Answer 39

Complications in ligand-receptor interactions include the complexity of the extracellular environment, presence of multiple receptors, and modulation of binding by other proteins/molecules. These factors can influence binding kinetics, specificity, and signaling outcomes, leading to diverse cellular responses.

Question 40

what is receptor down-regulation and how can it occur

Answer 40

Receptor down-regulation is a cellular adaptation where cells reduce the number of receptors on their surface in response to prolonged exposure to a ligand, leading to decreased responsiveness. This can occur through internalization of receptors or disruption of receptor coupling to signaling pathways, preventing over-response to prolonged ligand exposure and maintaining cellular homeostasis.

Question 41

how can receptor down-regulation occur and why is it important

Answer 41

Receptor down-regulation happen through either: - removal of receptors from the cell surface via receptor-mediated endocytosis - alteration of receptor affinity for the ligand through phosphorylation - modification of the receptor that prevents it from initiating cellular changes. These mechanisms are important and they help cells adapt to changing ligand concentrations and maintain cellular homeostasis.

Question 42

How do ligand-receptor interactions influence the design of synthetic ligands for receptor binding in pharmaceuticals

Answer 42

Ligand-receptor interactions play a crucial role in pharmaceuticals, and synthetic ligands can be designed to bind specifically to receptors without triggering signaling.

Question 43

What are antagonists and agonists in the context of pharmaceuticals, and how do they interact with receptors?

Answer 43

Antagonists are pharmaceuticals that inhibit receptors by preventing naturally occurring messengers from binding and activating the receptor. On the other hand, agonists are pharmaceuticals that activate the receptor they bind to.

Question 44

Can you provide examples of agonists and antagonists in the context of pharmaceuticals, and explain how they interact with specific receptors to elicit their effects?

Answer 44

Examples: - isoproterenol is an agonist that activates β-adrenergic receptors and is used to treat asthma and stimulate the heart. - Propranolol, on the other hand, is an antagonist that inhibits β-adrenergic receptors, reducing blood pressure and the strength of cardiac contractions. - - ---- - Famotidine is another example of an antagonist that inhibits histamine receptors in the stomach, commonly used to treat conditions like acid reflux.

Question 45

How do ligand-receptor interactions trigger signal transduction and regulate cellular responses in intracellular signaling pathways

Answer 45

Intracellular signaling involves ligand binding to a receptor, causing receptor activation and changes in cellular activities. This triggers a preprogrammed sequence of events inside the cell, known as signal transduction, which involves various molecular interactions. These pathways regulate cellular responses such as gene expression, protein synthesis, and cell growth.

Question 46

what is signal amplification and how does it attained, with an example

Answer 46

Signal amplification is a phenomenon where small quantities of ligand can trigger a dramatic cellular response. This is often achieved through signaling cascades, where each step activates multiple molecules for the next step. An example is the breakdown of glycogen in response to epinephrine.

Question 47

why is signal amplification needed

Answer 47

Signal amplification ensures efficient and sensitive cellular responses to external stimuli.

Question 48

How do small GTPases function as molecular switches in intracellular signaling pathways, and what are some examples of small GTPase families?

Answer 48

GTPases, also known as guanine nucleotide triphosphatases, act as molecular switches in cellular signaling. Small monomeric GTPases, often referred to as "Small GTPases," are important examples of this class of proteins. Examples of small GTPase families include Ras, Rho, Rab, Arf, and Ran.

Question 49

How are small GTPases different from heterotrimeric G-proteins

Answer 49

Unlike heterotrimeric G-proteins, which are directly activated by GPCRs (G-protein coupled receptors), small GTPases are monomeric and have distinct mechanisms of activation.

Question 50

why are small GTPases modified with lipid groups

Answer 50

Many small GTPases are also modified with lipid groups because they help to direct them to specific cellular membranes, where they play important roles in membrane trafficking, vesicular transport, and other cellular processes.

Question 51

how is GTPase localisation regulated, and why is the lipid groups important

Answer 51

GTPase localization is regulated by post-translational modifications, where a hydrophobic lipid groups, such as farnesyl or geranylgeranyl, is attached to the GTPase. This lipid group plays a crucial role in targeting the GTPase to specific cellular membranes, such as the golgi membrane or plasma membrane.

Question 52

why do lipid modifications occur

Answer 52

lipid modification can facilitate protein interactions, enabling the GTPase to engage with other proteins and participate in signaling pathways or other cellular processes.

Question 53

what are the 3 types of kinases

Answer 53

Three types of kinases are: * Protein kinases * Lipid kinases * Carbohydrate kinases

Question 54

through which mechanisms can kinase activation occur

Answer 54

Kinase activation can occur through various mechanisms, including: * Phosphorylation * Dephosphorylation * Binding of a ligand/activating protein * Regulation of localisation

Question 55

what counteracts the actions of kinases

Answer 55

Phosphatases counteract the actions of kinases. Kinases add phosphate groups to proteins, while phosphatases remove phosphate groups.

Question 56

what plays a key role in determining kinases specificity

Answer 56

The molecular structure of kinases plays a key role in determining their specificity in phosphorylating target proteins.

Question 57

what are second messengers and what do they do

Answer 57

Second messengers are small intracellular molecules that are synthesized or mobilized in response to the activation of a signaling pathway. They amplify and diversify the signal, acting as intermediates in intracellular signaling cascades.

Question 58

what are examples of second messengers

Answer 58

Examples of second messengers include: lipids such as IP3 (inositol trisphosphate) and PIP3 (phosphatidylinositol 3,4,5-trisphosphate), ions such as calcium and potassium, and nucleosides such as cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate).

Question 59

what are transcription factors, what is their function

Answer 59

Transcription factors are proteins that regulate the rate of transcription of target genes. They play a crucial role in gene expression, controlling when and how genes are turned on or off in response to various signals and cues. Transcription factors can either activate or repress the expression of their target genes, and some transcription factors can do both.

Question 60

why do transcription factors bind to specific DNA sequences

Answer 60

Transcription factors bind to specific DNA sequences called enhancers or promoters, and either activate or repress the transcription of target genes, thus controlling their expression levels.

Question 61

which mechanisms can regulate transcription factors

Answer 61

Transcription factors can be regulated through various mechanisms that can impact their activity and function. Some of the common mechanisms of transcription factor regulation include: - Altered expression - Phosphorylation/dephosphorylation - Binding an activator/ligand/corepressor/co-activator - Dimerization - Localisation to the nucleus

Question 62

what are protein kinases, and what are the 2 group types they can categorized into

Answer 62

Protein kinases are enzymes that add phosphate groups to proteins, called phosphorylation. They can be categorized into two types: >Tyrosine Kinases >Serine/Threonine Kinases

Question 63

what is phosphorylation and what is its function

Answer 63

Phosphorylation is a vital posttranslational modification and the most common mechanism for regulating protein function. It plays critical roles in regulating cellular processes such as the cell cycle, growth, apoptosis, and signal transduction pathways.

Question 64

where does phosphorylation occur

Answer 64

The most common phosphorylation sites are serine (Ser) and threonine (Thr) residues, followed by tyrosine (Tyr) residues. However, phosphorylation can also occur on other amino acids, such as arginine (Arg), histidine (His), aspartic acid (Asp), cysteine (Cys), glutamic acid (Glu), and lysine (Lys), although these are less common and referred to as non-canonical phosphorylation.

Question 65

what are RTKs, with examples

Answer 65

Receptor Tyrosine Kinases (RTKs) are a class of cell surface receptors that play important roles in cellular signaling. They include receptors such as the insulin receptor, nerve growth factor receptor, and epidermal growth factor (EGF) receptor. RTKs are typically composed of a single polypeptide chain with a single transmembrane domain.

Question 66

which region of RTKs is responsible for ligand binding

Answer 66

The extracellular region of RTKs is responsible for ligand binding.

Question 67

How do the kinase domain and tyrosine residues in the cytosolic region of receptor tyrosine kinases (RTKs) facilitate cellular signaling through autophosphorylation and protein docking

Answer 67

The cytosolic region of RTKs contains a kinase domain that has enzymatic activity to add phosphate groups to tyrosine residues in the receptor itself (autophosphorylation) and in downstream target proteins. The cytosolic tail of RTKs also contains multiple tyrosine residues that serve as docking sites for signaling proteins, allowing for the recruitment of downstream signaling molecules to propagate the signal.

Question 68

how is RTKs activated

Answer 68

Activation of Receptor Tyrosine Kinases (RTKs) typically involves the following steps: 1. Ligand binding: Ligand binding causes RTKs to aggregate. 2. Autophosphorylation: The cytosolic kinase domain of RTKs phosphorylates tyrosine residues on its own receptor in a process called autophosphorylation. 3. Transphosphorylation: Autophosphorylation creates docking sites for other signaling proteins, leading to phosphorylation of tyrosine residues on neighboring RTKs, a process called transphosphorylation. 4. Activation of downstream signaling pathways: Autophosphorylation and transphosphorylation trigger activation of downstream signaling pathways, leading to cellular responses to the ligand stimulus.

Question 69

what happens after RTKs are activated

Answer 69

Upon activation, Receptor Tyrosine Kinases (RTKs) recruit proteins containing the SH2 (Src Homology 2) domain, which is a structurally conserved protein interaction domain.

Question 70

what was SH2 domain initially identified as

Answer 70

The SH2 domain was initially identified in the Src oncoprotein.

Question 71

why does SH2 bind to phosphosphorylated tyrosine kinase residues in target protein

Answer 71

The SH2 domain specifically binds to phosphorylated tyrosine residues on target proteins, as it allows for the formation of protein-protein interactions and subsequent activation of downstream signaling pathways.

Question 72

what does recruitment of proteins containing SH2 domains by activated receptoe tyrosine kinases allow

Answer 72

Recruitment of proteins containing SH2 domains by activated Receptor Tyrosine Kinases (RTKs) allows for the activation of multiple signaling pathways simultaneously.

Question 73

what are 2 pathways that can be activated by RTKs through SH2 domain-mediated interactions

Answer 73

Two well-known pathways that can be activated by RTKs through SH2 domain-mediated interactions are the inositol-phospholipid-calcium pathway and the Ras pathway.

Question 74

how can RTKs activate Ras signalling pathway

Answer 74

Receptor Tyrosine Kinases (RTKs) can activate the Ras signaling pathway through the involvement of Ras and its regulators, including Sos (son of sevenless) and GAP (GTPase activating protein).

Question 75

what is Sos and how does it activate Ras

Answer 75

Sos is a guanine-nucleotide exchange factor (GEF) that activates Ras by binding to RTKs through GRB2.

Question 76

what is GAP and how does it promote inactivation of Ras

Answer 76

GAP is a GTPase activating protein that promotes Ras inactivation by stimulating GTP hydrolysis.

Question 77

what is Ras, and when is it active and inactive

Answer 77

Ras is a small G-protein that is active when bound to GTP, and inactive when bound to GDP.

Question 78

what is Ras-Raf-Mek-Erk signalling pathway

Answer 78

The Ras-Raf-Mek-Erk signaling pathway is a crucial cellular signaling cascade that regulates various cellular processes.

Question 79

In the Ras-Raf-Mek-Erk pathway, what activates what

Answer 79

- Ras activates Raf (MAP3K) - Raf activates Mek (MAP2K) - Mek activates Erk (MAPK)

Question 80

what is the function of Erk in Ras-Raf-Mek-Erk pathway

Answer 80

the function of Erk is to phosphorylate downstream proteins and thus regulate gene expression and cellular processes.

Question 81

what are GPCRs and how do they activate or inactivate specific G proteins and what do activated G proteins do

Answer 81

GPCRs are seven-pass transmembrane proteins that activate specific G proteins when bound to GTP and inactivate them when bound to GDP. Activated G proteins then bind to target proteins such as enzymes or channel proteins.

Question 82

what are examples of GPCRs

Answer 82

Examples of GPCRs include olfactory receptors, norepinephrine receptors, hormone receptors, and smoothened receptors.

Question 83

what are the diverse biological functions of GPCRs

Answer 83

The diverse biological functions of over 2000 human G protein-coupled receptors (GPCRs) are: smell, taste, light perception, neurotransmission, endocrine and exocrine gland function, chemotaxis, exocytosis, blood pressure regulation, embryogenesis, development, cell growth and differentiation, viral infection, and oncogenesis.

Question 84

what are the 6 classes can GPCRs be categorised into

Answer 84

GPCRs are categorized into 6 classes based on sequence homology and functional similarity: - Class A (or 1) - Rhodopsin-like - Class B (or 2) - Secretin receptor family - Class C (or 3) - Metabotropic glutamate/pheromone - Class D (or 4) - Fungal mating pheromone receptors - Class E (or 5) - Cyclic AMP receptors - Class F (or 6) - Frizzled/Smoothened

Question 85

what are the 2 families of G proteins

Answer 85

There are two families of G proteins: heterotrimeric G proteins and small monomeric G proteins. Heterotrimeric G proteins are large proteins consisting of three subunits (Gα, Gβ, and Gγ) and signal through 7-pass transmembrane receptors known as GPCRs. Small monomeric G proteins are smaller in size and do not require GPCRs for signaling.

Question 86

examples of small monomeric G proteins

Answer 86

Examples of small monomeric G proteins include the Ras family and Rho family.

Question 87

what is one of the major outcome of G protein activation

Answer 87

One of the major outcomes of G protein activation is the release or formation of second messengers, which are small molecules that transmit signals from the cell membrane to the interior of the cell.

Question 88

what are examples of second messengers

Answer 88

Examples of second messengers include: - lipids (such as inositol trisphosphate or IP3, phosphatidylinositol-3,4,5-trisphosphate or PIP3) - ions (such as calcium, potassium) - nucleosides (such as cyclic adenosine monophosphate or cAMP, cyclic guanosine monophosphate or cGMP).