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UVic BIOL 360 - Fall 2019 > Cell Signalling (ch15) > Flashcards

Cell Signalling (ch15) Flashcards

1
Q

What is an example of a unicellular organism responding to physical and chemical changes in its environment?

A

Saccharomyces cerevisia take on the “Schmoo” shape in response to chemical mating signal.

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2
Q

What is a gap junction?

A

A narrow, water-filled channel which directly connects adjacent cells.

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3
Q

What components form a gap junction?

A

6 connexins from each cell (12 total) form a tube called a connexon.

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4
Q

What differentiates a heteromeric connexon from a homomeric connexon?

A

Heteromeric: connexins are of different types
Homomeric: connexins are all the same type

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5
Q

What differentiates the structure of a homotypic gap junction from a heterotypic gap junction?

A

Homotypic: all connexins forming the connexons are of the same type
Heterotypic: connexins which form the connexons are of different types

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6
Q

What is a gap junction called in a plant cell?

A

A plasmodesmata.

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7
Q

List some examples of signal molecules.

A
  • Proteins
  • Peptides
  • Amino Acids
  • Nucleotides
  • Steroids
  • Retinoids
  • Fatty Acid Derivatives
  • Gases
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8
Q

In what 3 ways are extracellular signal molecules exposed to the extracellular space?

A
  1. Exocytosis
  2. Diffusion
  3. Attached to extracellular side of plasma membrane
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9
Q

What are examples of ways in which cells respond specifically to combinations of signals?

A

ABC might tell a cell to survive, while ABCD triggers division, ABCE causes differentiation, and no signal at all triggers apoptosis.

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10
Q

What are the 2 main types of receptors involved in cell-signalling?

A
  1. Cell-surface receptors

2. Intracellular receptors

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11
Q

How many distinct nuclear receptors do humans have?

A

48.

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12
Q

What is an “orphan” receptor.

A

A receptor whose function remains a mystery.

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13
Q

What are the 3 classes of cell-surface receptors?

A
  1. Ion-channel-coupled receptors
  2. G-protein-coupled receptors
  3. Enzyme-coupled receptors
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14
Q

What are the 4 types of cell signalling?

A
  1. Contact-dependent (juxtacrine)
  2. Paracrine (/autocrine)
  3. Synaptic
  4. Endocrine
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15
Q

What is the “fast” way cells react to signalling? What is the “slow” way?

A

Fast: alter protein function
Slow: alter protein synthesis

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16
Q

How can two different cells have different responses to the same signal ligand?

A

By having different receptors, signal cascade proteins, effector proteins, or by activating different genes.

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17
Q

What effect does acetylcholine have on a skeletal muscle cell?

A

Triggers contraction.

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18
Q

What effect does acetylcholine have on a heart pacemaker cell?

A

Reduces the rate of firing.

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19
Q

What effect does acetylcholine have on a salivary gland cell?

A

Triggers secretion.

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20
Q

How is it possible for 2 cells of the same type to respond differently to the same ligand?

A

Because of morphogen gradients which have varied concentrations of inducing or inhibiting factors.

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21
Q

Describe the 1º and 2º response when cells react to a signal by altering protein synthesis.

A

1º: synthesized protein stimulates response

2º: synthesized protein is transcription factor

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22
Q

What are some examples of small intracellular mediators/2º messengers?

A

Calcium, cAMP.

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23
Q

What are 3 major characteristics of small intracellular mediators/2º messengers?

A
  1. Generated in large numbers
  2. Diffuse away from source
  3. Alter protein conformation
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24
Q

What are 3 major characteristics of large intracellular signalling proteins/1º messengers?

A
  1. Are molecular switches
  2. Generate 2º messengers
    OR
  3. Activate next signal/effector protein
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25
Q

How is a proteins activation state modified by phosphorylation? What enzymes are involved?

A

Activation: phosphorylation by protein kinase
Deactivation: de-phosphorylation by protein phosphatase

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26
Q

How many protein kinases exist in the human genome? What about protein phosphatases?

A

Kinases: 520
Phosphatases: 150

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27
Q

What differentiates signalling by phosphorylation from signalling by GTP-binding?

A

Phosphorylation: protein is directly phosphorylated

GTP-binding: protein binds to GTP, which is phosphorylated

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28
Q

What 2 types of proteins are activated by GTP-binding?

A
  1. Large trimeric GTP-binding proteins (G-proteins)

2. Monomeric GTP-binding proteins

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29
Q

How do scaffold proteins facilitate signal transduction?

A

It holds the intracellular signal proteins so that they are in position to activate downstream messengers. Decreases cross-talk.

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30
Q

What is a signalling complex? How do they associate with receptors?

A

Receptor itself can act as a scaffold protein by allowing signalling proteins to bind to phosphorylation sites on the activated receptor.

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31
Q

What is a “transient” signalling complex?

A

A complex which is rapidly assembled upon activation but which is immediately disassembled.

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32
Q

What is an “all-or-none” signal response?

A

Exactly how it sounds. If the threshold isn’t met no activation occurs.

33
Q

What is a “hyperbolic” signal response?

A

The signal response is initially strong but loses intensity over time.

34
Q

What is a “sigmoidal” signal response?

A

The signal response is slow at first, then accelerates rapidly before eventually losing intensity.

35
Q

In what 5 ways can desensitization occur?

A
  1. Receptor sequestration
  2. Receptor down-regulation
  3. Receptor inactivation
  4. Signal protein inactivation
  5. Production of inhibitory protein
36
Q

How many types of G-Protein coupled receptors do humans have?

A

> 800 (150 orphan).

37
Q

How many types of G-Protein coupled receptors do mice have that are responsible for smell alone?

A

~1000.

38
Q

Describe the structure of a G-Protein coupled receptor.

A

7 transmembrane domains with an extracellular binding site.

39
Q

Describe the structure of a G-Protein. Which of these structures binds GDP/GTP?

A

Heterotrimeric, with α, β, and γ subunits. The α subunit binds GDP/GTP.

40
Q

What percentage of drugs target G-Protein coupled receptors?

A

~50%.

41
Q

What protein stimulates the production of cAMP when activated?

A

Adenylyl cyclase.

42
Q

What is required for cAMP to produce a rapid response?

A

Rapid synthesis and rapid breakdown.

43
Q

Do all G-Protein coupled receptors and G-Proteins stimulate adenylyl cyclase?

A

No. Some can have an inhibitory effect on adenylyl cyclase.

44
Q

What are some examples of hormonal responses which are mediated by the G-Protein stimulated increase in cAMP?

A

Increased concentration of:

  • TSH
  • ACTH
  • LH
  • Adrenaline
  • Parathormone
  • Glucagon
  • Vasopressin
45
Q

Outline the pathway through which G-Protein coupled receptors have downstream non-nuclear effects via cAMP.

A

GPCR > G-Protein > AC > cAMP > PKA > downstream effects (ion channels, GTPases, target proteins, etc)

46
Q

Outline the pathway through which G-Protein coupled receptors have downstream nuclear effects via cAMP.

A

GPCR > G-Protein > AC > cAMP > PKA > (nucleus) > CREB > gene transcription

47
Q

What are the major results of phospholipase C activation by G-Protein-mediated increase in [cAMP]?

A
  1. Stimulates IP₃ to trigger release of Ca2+ from the ER

2. Stimulates diacylglycerol to activate PKC

48
Q

What protein acts as an intracellular mediator of calcium? How does it interact with calcium?

A

Calmodulin. Has NH₂ and COOH domains which each bind 2 calcium ions.

49
Q

How does calmodulin activate other proteins?

A

Can wrap around target proteins to activate them but only when bound to 4 calcium ions.

50
Q

What is the structure of the calcium/calmodulin-dependent kinase (CaM-kinase)? What is its purpose?

A

Two stacked rings with 6 kinase domains. Somehow involved in memory and learning in vertebrates.

51
Q

How can G-Proteins directly regulate ion channels?

A

Inhibitory G-Proteins can have an α subunit which inhibits adenylyl cyclase while the βγ subunit opens potassium channels. (example)

52
Q

How can G-Proteins indirectly regulate ion channels?

A

By moderating the level of cAMP, which is itself able to open or close ion channels. (example: sodium channels)

53
Q

In what 3 ways can G-Protein coupled receptors be desensitized?

A
  1. Receptor inactivation
  2. Receptor sequestration
  3. Receptor downregulation
54
Q

How do arrestin and GPCR kinase (GRK) interact with G-Protein coupled receptors?

A

GRK phosphorylates the GPCR across multiple sites, allowing arrestin to bind and prevent further signalling.

55
Q

What are the 6 types of enzyme-coupled cell-surface receptors?

A
  1. Receptor tyrosine kinases (RTKs)
  2. Tyrosine-kinase associated receptors (cytokine receptors)
  3. Receptor serine/threonine kinases
  4. Histidine-kinase-associated receptors
  5. Receptor guanylyl cyclases
  6. Receptorlike tyrosine phosphatases
56
Q

What do all the other receptor tyrosine kinases have in common that insulin receptor (IGF1) does not share?

A

All the TRKs must dimerize and autophosphorylate each other to activate while the IGF1 receptor is already a dimer.

57
Q

How is the EGF receptor tryrosine kinase (RTK) different from the other RTKs?

A

EGF also dimerizes but instead of both RTKs autophosphorylating, one “receiver” does all the work while the “activator” gets phosphorylated for free.

58
Q

During insulin receptor (IGF1) (receptor tryrosine kinase) activation, what is the function of IRS1?

A

A scaffold protein which binds to the receptor and has multiple phosphorylation sites to allow binding of other proteins.

59
Q

What other proteins are associated with IRS1 (an insulin receptor IGF1 scaffold protein).

A

Grb2, an adaptor protein which binds Sos and another scaffold protein.

60
Q

Describe the structure of Grb2, an adaptor protein involved in insulin receptor IGF1 activation.

A

One SH2 domain which binds to IRS1 (docking protein) and two SH3 domains which bind to Sos and scaffold proteins.

61
Q

What is the function of GTPase Ras? What is it stimulated by? What are its downstream effects?

A

To mediate receptor tyrosine kinase signalling. Stimulated by Ras-GEF (Sos). Activates MAPKKK (Raf) > MAPKK (Mek) > MAPK (Erk) > altered protein activity and gene expression.

62
Q

How do you avoid cross-talk between parallel MAP kinase modules in the cell?

A

Employing scaffold proteins (which may or may not have their own kinase domains).

63
Q

Why do we need the MAPK pathway?

A

Because the Ras signal only persists for 3 minutes.

64
Q

How can receptor tyrosine kinases (RTKs) influence membrane-bound phosphoinositides (PIPs)?

A

By activating Phosphoinositide 3-kinase which can phosphorylate PIPs and change their binding characteristics with other proteins.

65
Q

Outline the tyrosine kinase (RTK) and phosphoinositide 3-kinase (PI 3-kinase) pathway.

A

RTK > PI 3-Kinase > PI(4,5)P₂ becomes PI(3,4,5)P₃ > PDK1 > Akt > mTOR > active Akt > Bad

66
Q

In the tyrosine kinase (RTK) and phosphoinositide 3-kinase (PI 3-kinase) pathway, what is the function of Bad?

A

Bad inactivates apoptosis-inhibitory protein. When phosphorylated by Akt, Bad is inactivated and apoptosis-inhibitory protein can function.

67
Q

What is an example of a tyrosine-kinase associated receptor?

A

A cytokine receptor or Janus kinase.

68
Q

What is the downstream effect of a Janus kinase (JAK)? What protein is activated by JAK directly? Where does this protein go?

A

To alter gene transcription. Activates STAT1 which is translocated to the nucleus as a dimer.

69
Q

How many protein tyrosine phosphatases do humans have?

A

~100.

70
Q

What is the purpose of Notch signalling?

A

During development, involved in cell differentiation. Signals surrounding cells not to differentiate.

71
Q

Is the activation of a Notch receptor reversible?

A

No. Differentiation is a permanent process.

72
Q

Where are Notch ligands expressed in the body? Where are the receptors?

A

Notch ligands are expressed on the surface of signalling cells and must come into direct contact with receptors on the surface of target cells.

73
Q

What protein do SH2 domains bind to?

A

Short amino acid sequences containing a phosphotyrosine.

74
Q

Why does CaM-kinase 2 have prolonged activity after activation?

A

It traps bound calcium/calmodulin until cytosolic levels are normal and it must be dephosphorylated to be inactivated.

75
Q

Besides the cytoskeleton, what type of proteins make good drug targets?

A

Scaffold proteins.

76
Q

What kind of transporter is an acetylcholine receptor at a neuromuscular junction?

A

An acetylcholine-gated cation channel. Allows Na⁺ into the cell.

77
Q

What activates a G-protein during cell signalling?

A

A G-protein coupled receptor (GPCR).

78
Q

What kind of signalling pathway is activated in response to an odorant?

A

A GPCR activates a G-protein with downstream effects.

79
Q

What is remarkable about the Notch signalling pathway?

A

It is the simplest intracellular pathway which is activated at the membrane and has effects on the nucleus.

UVic BIOL 360 - Fall 2019 (10 decks)

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