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Biochemistry Exam 3 > Lecture 2: Cell signaling > Flashcards

Lecture 2: Cell signaling Flashcards

1
Q

What are the 3 steps of cell signaling and what do they do?

A

Reception: target cell senses the substance in its exogenous environment. (intercellular signaling)

Transduction: Conversion of the signal via a cascade of molecular events (intracellular signaling)

Response: specific cellular effect attributed to the signaling molecule

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2
Q

What are the reception modes of intercellular signaling?

A

Juxtacrine, Endocrine, Synaptic, Paracrine and Autocrine

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3
Q

What is contact-dependent intercellular signaling?

A

Requires cells to make physical contact with one another (receptor contact)

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4
Q

What is contact-independent intercellular signaling?

A

Cells do not make physical contact

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5
Q

Which reception mode of intercellular signaling is contact-dependent?

A

Juxtacrine (Lecture 2 slide 45)

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6
Q

Which reception mode of intercellular signaling is contact-independent?

A

Endocrine, Synaptic, Paracrine, Autocrine

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7
Q

Which mode of intercellular signaling target receptors reached through bloodstream?

A

Endocrine

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8
Q

What does the endocrine mode of intercellular signaling do?

A

Target receptors reached through the bloodstream

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9
Q

Which mode of intercellular signaling target receptors on nearby cells?

A

Paracrine

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10
Q

What does the paracrine mode of intercellular signaling do?

A

Target receptors on nearby cells

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11
Q

Which mode of intercellular signaling targets receptors using an electrical signal?

A

Synaptic

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12
Q

What does the synaptic mode of intercellular signaling do?

A

Targets receptors using an electrical signal

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13
Q

Which mode of intercellular signaling targets receptors on the same cell?

A

Autocrine

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14
Q

What does the autocrine mode of intercellular signaling do?

A

Targets receptors on the same cell

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15
Q

Is transduction cell signaling intracellular or intercellular?

A

Intracellular

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16
Q

Is reception cell signaling intracellular or intercellular?

A

Intercellular

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17
Q

What are the 2 properties tissues capable of responding to hormones have in common?

A

1) Posses a receptor having a very high affinity for hormone
2) the receptor is coupled to a process that regulates the metabolism of the target cells.

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18
Q

What are the secreted molecules (ligand) during transduction?

A

Hormones: peptide hormones, sterioid hormones
Neurotransmitters
Peptides
Lipids

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19
Q

List the intracellular receptors (receptors for secreted molecules)

A

Steroid hormones, estrogen, androgen

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20
Q

List the cell surface receptors (receptors for secreted molecules)

A

Peptide hormones, growth factors

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21
Q

What are the steroid hormone receptors?

A

Glucocorticoid receptor, estrogen receptor

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22
Q

Where is the glucocorticoid receptor located and what does it do?

A

Cytosol
Upon binding to a glucocorticoid, it translocates into the nucleus and activates transcription of a gene

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23
Q

Where is the estrogen receptor located and what does it do?

A

Nucleus
Upon binding to the hormone, it activates transcription

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24
Q

What are the 2 types of steroid hormone receptor activities?

A

Genomic action = slow (minutes): lasts longer
Non-genomic action = rapid (seconds): simple turn on and off

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25
Q

What is estrogen synthesized from?

A

Cholesterol

26
Q

What are the major subtypes of estrogen receptors?

A

ERα and ER (beta)

27
Q

What do ERα and ER beta do?

A

Exert differential effects on growth and differentiation in tissues

28
Q

Where are estrogen receptors found?

A

All over the body (CNS, breast, liver, bone, cardiovascular system, GI tract, urogenital tract)
TA Lecture 1 Part B, slide 10

29
Q

What is SERM?

A

ER ligands which exhibit antagonistic or agonistic activity depending on the tissue

30
Q

What do SERM (Selective Estrogen Receptor Modulators) do?

A

Induce structural changes, affect the ability to interact with cofactors, different effects gene expression

31
Q

What drug is the 1st SERM used in clinic and what is it used for?

A

Tamoxifen (non-steroidal), used in ERα positive breast cancer

32
Q

Is Tamoxifen an antagonist or agonist receptor in the breast?

A

Antagonist
TA Lecture 2 Part A, slide 11

33
Q

Is Tamoxifen an antagonist or agonist receptor in the uterine?

A

Agonist
TA Lecture 2 Part A, slide 11

34
Q

What are examples of cell surface receptors?

A

Growth factors, EGF (epidermal growth factor), insulin

35
Q

All receptors are what type of receptors?

A

Transmembrane

36
Q

What type of hormones bind to cell surface receptors?

A

Hydrophilic

37
Q

What activates secondary messengers within the cell?

A

The binding of the hormone to its receptors

38
Q

The activation of secondary messengers within the cell leads to ______ ______.

A

signal transduction

39
Q

What are the 3 domains of cell surface receptors?

A

Extracellular, Transmembrane, Intracellular

40
Q

What are the major classes of transmembrane receptors?

A

1) Ligand-gated ion channels
2) Enzyme-linked receptor
3) Cytokine receptors
4) GPCR (G-protein coupled receptors)

41
Q

What happens in ligand-gated ion channels?

A

ligand binds to receptor, causing a change in membrane potential
TA Lecture 2 Part A, slide 15

42
Q

Explain enzyme-linked receptor (Tyrosine Kinase) pathway

A

1) Receptors activate tyrosine kinase or serine/threonine kinase activity in the cytoplasmic domain of the receptor
2) This leads to phosphorylation of intracellular signaling molecules and signal transduction
Has intrinsic kinase activity

Lectures 1&2, slide 63-65
TA Lecture 2 Part A, slide 17

43
Q

Explain Tyrosine Kinase with RAS GTPase

A

1) Growth factor binds to ligand binding site
2) Upon binding, tyrosine kinase receptors dimerize
3) Dimerization activates tyrosine kinase phosphorylation
4) Adaptor protein binds to phosphate and recruits ras-activating protein
5) Ras bound to GDP = inactive, Ras bound to GTP = active
6) Active Ras goes on to downstream signaling pathways (MAP kinases)

TA Lecture 2A, slide 19

44
Q

What do cytokine receptors not have? What pathway are they associated with?

A

Do not have intrinsic kinase activity, associated with protein kinase family (JAK-STAT)

45
Q

Explain the JAK-STAT pathway

A

1) Cytokine (IL-6, NF𝜅B, IFN𝜶) binds to the cytokine receptor
2) Activated cytokine receptors recruit JAK to the cytoplasmic domain
3) JAK phosphorylates tyrosine kinase receptors
4) STAT bind to phosphorylated tyrosine kinase receptors
5) Activated/phosphorylated STATs dimerize and translocate to the nucleus = activate transcription genes

TA Lecture 2B, slide 2

46
Q

Provide examples of cytokines

A

IL-6, NF𝜅B, IFN𝜶

47
Q

Which receptors is the most common receptors?

A

G-Protein Coupled Receptors

48
Q

How many transmembrane domain receptors does GPCR have?

A

7

49
Q

What are the 4 subclass types of G-proteins? What do they do?

A

𝜶i - inhibits adenyl cyclase = decreases cAMP, phospholipases, phosphodiesterases
𝜶s - stimulates adenyl cyclase = increase cAMP
𝜶q - activates phospholipase C
𝜶l2 - Rho GEFs

50
Q

In the GPCR signaling cascade, what does cAMP activate?

A

Protein kinase A

51
Q

In the GPCR signaling cascade, which enzyme breaks down cAMP?

A

Phosphodiesterase

52
Q

In the GPCR signaling cascade, phospholipase activates the conversion of _____ to ____ and ____.

A

PIP2 to DAG and IP3

53
Q

In the GPCR signaling cascade, DAG activates what?

A

PKC (protein kinase C)

54
Q

In the GPCR signaling cascade, what does IP3 cause?

A

The release of Ca+2 from ER

55
Q

Provide examples of secondary messengers

A

Ca2+ ion, 3’,5’-cyclic AMP, 3’, 5’ cyclic GMP, DAG, IP3

56
Q

What are the two ways PKC can be amplified?

A

G-protein linked receptor or Receptor tyrosine kinase

57
Q

Explain the modes of downregulation

A

a) Receptor inactivation - active receptor leads to signaling cascade, desensitized receptor leads to uncoupling from signaling cascade
b) Receptor internalization - receptor internalized and recycled
c) Receptor down-regulated - receptor internalized and degraded

58
Q

What drug is used to treat HER2-positive breast cancer?

A

Herceptin (Trastuzumab)

59
Q

How does Herceptin work?

A

Herceptin attaches to HER2 receptors and blocks it which inhibits the cells to grow and divide

60
Q

How do antibody conjugates work?

A

Use antibody to find target antigen and bind to lymphoma cell, thus allowing toxin to kill lymphoma cell

Biochemistry Exam 3 (4 decks)

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