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Y1 Cellular Biochemistry and Biology > L18: Cell Signalling > Flashcards

L18: Cell Signalling Flashcards

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1
Q

What is the general principle of signal transduction in cells?

A

Signals, often occurring outside the cell, are transduced and interpreted inside the cell, allowing the cell to respond appropriately.

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2
Q

Name four main types of cell signalling based on distance.

A
  1. Endocrine: Long-distance (e.g., hormones like insulin).
  2. Paracrine: Signals to nearby cells.
  3. Neuronal: Via neurotransmitters.
  4. Contact-dependent: Direct cell-to-cell contact.
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3
Q

What role do receptors play in cell signalling?

A

Receptors detect specific signals and initiate signal transduction, converting the extracellular signal into an intracellular response.

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4
Q

How do the same signals elicit different responses in various cells?

A

Responses depend on the receptor type and intracellular machinery unique to each cell.

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5
Q

What happens to a cell if it receives no survival signals?

A

It undergoes apoptosis (programmed cell death).

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6
Q

Differentiate between fast and slow cellular responses to signals.

A

• Fast responses: Modify existing proteins (e.g., phosphorylation).
• Slow responses: Involve transcription and translation, requiring new proteins to be made.

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7
Q

What are protein kinases, and what do they do?

A

Protein kinases are enzymes that phosphorylate proteins on serine, threonine, or tyrosine residues, altering their activity or creating docking sites.

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8
Q

What is the function of GTPases in cell signalling?

A

GTPases act as molecular switches, cycling between an active (GTP-bound) and inactive (GDP-bound) state to regulate signalling pathways.

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9
Q

Describe G-protein-coupled receptors (GPCRs).

A

GPCRs are cell surface receptors that span the membrane 7 times and, upon activation by a ligand, signal through trimeric G-proteins to initiate cellular responses.

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10
Q

What are second messengers? Provide examples.

A

Second messengers amplify and distribute signals within the cell. Examples include cyclic AMP (cAMP) and calcium ions.

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11
Q

Outline the role of phospholipase C (PLC) in signal transduction.

A

PLC cleaves PIP2 into DAG (diacylglycerol) and IP3 (inositol triphosphate), which respectively activate protein kinase C and release intracellular calcium.

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12
Q

What is the significance of the Ras protein in cell signalling?

A

Ras is a GTPase that activates downstream kinases in the MAPK pathway, driving processes like cell proliferation.

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13
Q

What is receptor tyrosine kinase (RTK) signalling?

A

RTKs, activated by dimerisation and autophosphorylation upon ligand binding, recruit adaptor proteins to propagate intracellular signals.

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14
Q

What are examples of clinical applications derived from signalling pathway knowledge?

A

• Herceptin (trastuzumab): Targets HER2-positive breast cancer.
• Vemurafenib: Inhibits mutant BRAF in metastatic melanoma.

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15
Q

What are the three main types of cell surface receptors?

A
  1. Ion channel-coupled receptors.
  2. G-protein-coupled receptors (GPCRs).
  3. Enzyme-coupled receptors (e.g., receptor tyrosine kinases).
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16
Q

How does cortisol mediate its effects?

A

Cortisol, a steroid hormone, diffuses across the plasma membrane, binds to an intracellular receptor, and together they regulate gene transcription in the nucleus.

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17
Q

What is the role of nitric oxide (NO) in cell signalling?

A

NO diffuses across membranes, affecting smooth muscle cells to regulate vascular tone and blood pressure.

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18
Q

What is the function of cyclic AMP (cAMP) in signalling?

A

cAMP, generated from ATP by adenylyl cyclase, acts as a second messenger to activate protein kinase A (PKA) and regulate various cellular processes.

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19
Q

How is cAMP signalling terminated?

A

cAMP is degraded to AMP by cyclic AMP phosphodiesterase, switching off the signal.

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20
Q

Explain the concept of a kinase cascade using the MAPK pathway.

A

In the MAPK pathway:
• Ras activates Raf.
• Raf phosphorylates MEK.
• MEK phosphorylates ERK (MAPK).
• ERK activates transcription factors to promote cell cycle progression.

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21
Q

What are the two main outcomes of calcium signalling?

A
  1. Activation of calcium-responsive proteins like calmodulin.
  2. Regulation of processes like muscle contraction, secretion, and enzyme activity.
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22
Q

What happens during the activation of receptor tyrosine kinases (RTKs)?

A

Ligand binding causes dimerization of RTKs, activating their kinase domains, leading to autophosphorylation and recruitment of adaptor proteins.

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23
Q

What is the role of Grb2 in RTK signalling?

A

Grb2 is an adaptor protein that binds phosphorylated tyrosine’s on RTKs and recruits SOS, a Ras-activating protein.

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24
Q

Why is Ras commonly mutated in cancer?

A

Mutations in Ras often prevent its GTPase activity, locking it in an active state, leading to uncontrolled cell proliferation.

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25
Q

What are the products of phospholipase C (PLC) activity, and what do they do?

A

• DAG (diacylglycerol): Activates protein kinase C (PKC).
• IP3 (inositol triphosphate): Triggers calcium release from intracellular stores.

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26
Q

What is the function of protein kinase C (PKC)?

A

PKC phosphorylates various target proteins, regulating processes such as metabolism, gene expression, and cell motility.

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27
Q

What is the role of calmodulin in calcium signalling?

A

Calmodulin binds calcium, undergoes a conformational change, and activates target proteins or enzymes involved in signalling.

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28
Q

How do cells integrate multiple signalling pathways?

A

Cells use signalling proteins modified by multiple post-translational modifications (e.g., phosphorylation) to integrate inputs from different pathways into a coordinated response.

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29
Q

How does HER2 amplification affect breast cancer prognosis?

A

HER2 amplification leads to increased proliferation of breast cancer cells and correlates with a poor prognosis, treatable with Herceptin (trastuzumab).

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30
Q

What is vemurafenib, and what mutation does it target?

A

Vemurafenib is a drug targeting mutant BRAF in metastatic melanoma, inhibiting aberrant MAPK pathway activation.

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31
Q

What are examples of long-distance and local signalling in the body?

A

• Long-distance: Hormonal signalling, e.g., insulin.
• Local: Paracrine signalling, e.g., delta-notch signalling during cell differentiation.

32
Q

What is the primary function of delta-notch signalling?

A

Delta-notch signalling ensures that neighbouring cells adopt different fates, such as during nerve cell differentiation.

33
Q

What is the difference between hydrophobic and hydrophilic signalling molecules?

A

• Hydrophobic molecules (e.g., steroid hormones): Diffuse across membranes to bind intracellular receptors.
• Hydrophilic molecules: Bind to cell surface receptors as they cannot cross the membrane.

34
Q

Why do cells require survival signals?

A

Survival signals prevent apoptosis, ensuring that cells remain functional.

35
Q

How do cells produce rapid responses to signals?

A

Rapid responses use pre-existing proteins modified through mechanisms like phosphorylation.

36
Q

What are two main enzymes that regulate phosphorylation states in proteins?

A
  1. Protein kinases: Add phosphate groups.
  2. Protein phosphatases: Remove phosphate groups.
37
Q

What are the key steps in the activation of heterotrimeric G-proteins?

A
  1. Ligand binds GPCR, causing conformational change.
  2. GDP is exchanged for GTP on the alpha subunit.
  3. The alpha subunit dissociates from the beta-gamma complex, activating downstream targets.
38
Q

What is the role of the beta-gamma complex in G-protein signalling?

A

The beta-gamma complex can interact with ion channels or other targets to propagate the signal.

39
Q

How does acetylcholine act on different cell types?

A

• Heart muscle: Slows heart rate via GPCRs.
• Salivary glands: Triggers saliva secretion.
• Skeletal muscle: Causes contraction via a different receptor.

40
Q

What is the effect of protein kinase A (PKA) activation by cAMP?

A

PKA phosphorylates target proteins, regulating processes like glycogen breakdown, transcription, and heart muscle contraction.

41
Q

How does inositol triphosphate (IP3) function in calcium signalling?

A

IP3 binds to receptors on the endoplasmic reticulum, causing the release of stored calcium into the cytosol.

42
Q

What is diacylglycerol (DAG), and what is its role in signalling?

A

DAG remains in the membrane and activates protein kinase C (PKC), which phosphorylates target proteins.

43
Q

What is the significance of Ras conformational changes?

A

Ras changes shape upon GTP binding, allowing it to activate downstream effectors in pathways like the MAPK cascade.

44
Q

What proteins are activated by Ras in the MAPK pathway?

A
  1. Raf (MAPKKK).
  2. MEK (MAPKK).
  3. ERK (MAPK), which enters the nucleus to regulate transcription.
45
Q

What cellular processes does ERK regulate?

A

ERK phosphorylates transcription factors, driving gene expression required for cell cycle progression.

46
Q

What are the two products of phosphatidylinositol 4,5-bisphosphate (PIP2) cleavage by phospholipase C?

A
  1. IP3: Mobilizes calcium.
  2. DAG: Activates PKC.
47
Q

What is the significance of protein location in signalling pathways?

A

Many signalling proteins, such as Ras and G-proteins, are membrane-associated, which helps localize and regulate their activity.

48
Q

What are post-translational modifications, and why are they important?

A

Modifications like phosphorylation or acetylation integrate multiple signals and determine a protein’s activity or interactions.

49
Q

How does Herceptin (trastuzumab) work in HER2-positive breast cancer?

A

It blocks HER2 signalling and recruits the immune system to attack cancer cells.

50
Q

What mutation does vemurafenib target, and in which cancer is it used?

A

Vemurafenib targets the BRAF V600E mutation, commonly found in metastatic melanoma.

51
Q

What is the primary transduction step in signal transduction pathways?

A

It involves the initial transmission of a signal from the outside of the cell through the plasma membrane via a receptor.

52
Q

How do steroid hormones like cortisol enter cells, and what do they affect?

A

Steroid hormones diffuse across the plasma membrane, bind intracellular receptors, and regulate gene transcription.

53
Q

How does nitric oxide (NO) affect vascular tone?

A

NO diffuses into smooth muscle cells, altering their contractility and thereby regulating blood pressure.

54
Q

What is the function of primary messengers compared to second messengers?

A

• Primary messengers: External signals that bind receptors (e.g., hormones, neurotransmitters).
• Second messengers: Intracellular molecules like cAMP and calcium that amplify and distribute the signal.

55
Q

How does protein phosphorylation affect protein function?

A

Phosphorylation can change protein conformation, alter its activity, or create docking sites for other proteins.

56
Q

What is a key difference between protein kinases and protein phosphatases?

A

Kinases add phosphate groups to proteins, while phosphatases remove them, both regulating protein activity.

57
Q

What role does the alpha subunit of heterotrimeric G-proteins play?

A

The alpha subunit binds GDP/GTP and, when activated (GTP-bound), separates from the beta-gamma complex to propagate signals.

58
Q

Describe an example of a G-protein signalling pathway that involves ion channels.

A

In heart cells, the beta-gamma complex of a G-protein opens potassium channels, slowing the heart rate.

59
Q

What are two main types of molecules that activate GPCRs?

A

GPCRs can be activated by a wide variety of ligands, including peptides, small molecules, and even light in the case of rhodopsin.

60
Q

What is the role of calcium as a second messenger?

A

Calcium regulates processes like muscle contraction, secretion, and activation of calcium-responsive proteins like calmodulin.

61
Q

What is the importance of the Ras-MAPK pathway in cell signalling?

A

It regulates cell proliferation by transmitting signals from receptor tyrosine kinases to transcription factors in the nucleus.

62
Q

How does the activation of Ras occur?

A

A guanine exchange factor (e.g., SOS) facilitates the exchange of GDP for GTP on Ras, activating it.

63
Q

What is the role of the adaptor protein Grb2 in RTK signalling?

A

Grb2 binds phosphorylated tyrosines on RTKs and recruits SOS to activate Ras.

64
Q

How do receptor tyrosine kinases (RTKs) initiate intracellular signalling?

A

Ligand binding induces dimerization and autophosphorylation of RTKs, creating docking sites for signalling proteins.

65
Q

What are PIP2, IP3, and DAG, and how are they related?

A

PIP2 is a phospholipid cleaved by phospholipase C to produce IP3 and DAG, which act as second messengers.

66
Q

How does IP3 contribute to intracellular calcium release?

A

IP3 binds to receptors on the endoplasmic reticulum, opening calcium channels and releasing stored calcium into the cytosol.

67
Q

What is the importance of diacylglycerol (DAG) in signalling?

A

DAG activates protein kinase C (PKC), which phosphorylates various substrates to regulate cell functions.

68
Q

Why is calcium signalling visualized as a wave during fertilization?

A

Calcium release spreads across the egg, ensuring uniform activation and cellular changes necessary for development.

69
Q

What is the functional significance of calmodulin in calcium signalling?

A

Calmodulin binds calcium, changes conformation, and activates target proteins, playing a critical role in signal transduction.

70
Q

What is the function of phospholipase C in the context of G-protein signalling?

A

Phospholipase C cleaves PIP2 into DAG and IP3, which together trigger further signalling cascades.

71
Q

Why is Ras considered an oncogene?

A

Mutations in Ras prevent it from hydrolyzing GTP, locking it in an active state and driving unregulated cell division.

72
Q

What is the significance of phosphorylation in signal integration?

A

Phosphorylation integrates multiple signals by modifying proteins to create complex cellular responses.

73
Q

How is the MAPK pathway involved in cancer therapy?

A

Drugs like vemurafenib target mutations in components like BRAF to block abnormal MAPK signalling in cancers like melanoma.

74
Q

What is the role of protein kinase C (PKC) in signalling?

A

PKC, activated by DAG and calcium, phosphorylates various proteins, influencing cell growth, differentiation, and apoptosis.

75
Q

How do growth factors influence receptor tyrosine kinases (RTKs)?

A

Growth factors bind RTKs, causing dimerization and phosphorylation, which initiate downstream signalling pathways.

Y1 Cellular Biochemistry and Biology (20 decks)

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