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MCM Exam 2 > (4) Receptors and Cell Signaling > Flashcards

(4) Receptors and Cell Signaling Flashcards

1
Q

What are the 4 types of signaling?

A
  • Endocrine
  • Paracrine
  • Autocrine
  • Juxtacrine
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2
Q

Describe ENDOCRINE signaling

A

Signal (hormone) is transported via blood

  • Long distance signaling
  • Long lasting
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3
Q

What is an example of endocrine signaling?

A

Epinephrine

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4
Q

Describe PARACRINE signaling

A

Signal (paracrine factor) diffuses to neighboring target cell of a different cell type

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5
Q

What is an example of PARACRINE signaling?

A

Testosterone

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6
Q

Describe Autocrine signaling

A

Secreting cells express surface receptors for the signal (aka, release to cells of same type)

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7
Q

What is an example of Autocrine signaling?

A

Interleukin-1

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8
Q

Describe Direct/Juxtacrine signaling

A

Signal binds to signaling cell which then binds to receptor on the target cell

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9
Q

What is an example of direct/juxtacine signaling?

A

Heparin-binding epidermal growth factor

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10
Q

CORRELATION BOX:

What does Insulin do?

A
  • Lowers blood glucose by promoting glycolysis
  • Inhibits gluconeogenesis
  • Stimulates glycogen synthesis
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11
Q

CORRELATION BOX:

What does glucagon do?

A
  • Increases blood sugar by promoting breakdown of glycogen in liver
  • Inhibits glycogen synthesis
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12
Q

CORRELATION BOX:

What does Epinephrine do?

A

Stimulates glycogen breakdown by promoting glucagon secretion

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13
Q

CORRELATION BOX:

Cortisol?

A

Stimulates gluconeogenesis

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14
Q

CORRELATION BOX:

What is GRAVES disease biochemical impact?

A
  • Autoimmune disorder
  • Thyroid stimulating immunoglobin (TSI) binds to and OVERSTIMULATES TSH receptors –> HYPERTHYROIDISM
  • Decreased TSH, Increased T3 and T4
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15
Q

CORRELATION BOX:

What is GRAVES disease symptoms?

A
  • Most common amongst women, presents by 40

- Weight loss, tachycardia, insomnia, ppretibial myxedema, opthalmopathy, thyroid goiter

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16
Q

CORRELATION BOX:

What is GRAVES disease TREATMENT?

A
  • Surgical resection of the thyroid gland
  • Radioactive Iodine
  • Pharmacological intervention
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17
Q

What are the types of signaling molecules?

A
  • Water soluble (hydrophilic)

- Lipid soluble (hydrophobic)

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18
Q

Hydrophilic Signaling:

How does the signal communicate with the receptors?

A

Interacts with receptors at the CELL SURFACE

*can’t penetrate pm

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19
Q

Hydrophilic Signaling:

What are examples?

A

Epinephrine
Insulin
Glucagon

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20
Q

Hydrophilic Signaling:

What happens after signal binds to receptor?

A

Initiates production of second messenger molecules inside cell

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21
Q

Hydrophilic Signaling:

What are examples of receptors involved in hydrophilic signaling?

A
  • G-protein coupled receptors (GPCRs)

- Receptor tyrosine kinases (RTKs)

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22
Q

Lipophilic Signaling:

How do lipophilic signals interact with their receptors?

A

Pass through pm of target cell

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23
Q

Lipophilic Signaling:

What are examples of lipophilic signaling hormones?

A
  • Steroid hormones
  • Thyroid hormones
  • Retinoids
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24
Q

Lipophilic Signaling:

Signaling molecule-receptor complex acts as…

A

transcription factor

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25
Q

What are the three classes of receptors?

A
  1. Ligand-gated ion channels
  2. G protein-coupled receptors
  3. Enzyme-coupled receptor class: receptor tyrosine kinases (RTKs)
26
Q

CORRELATION BOX: Lipophilic and Hydrophilic Hormone Medications

Give example of Hydrophilic medication

A

*short half lives

Epinephrine ; given at time of need

27
Q

CORRELATION BOX: Lipophilic and Hydrophilic Hormone Medications

Give example of Lipophilic medication

A

*long half lives

Oral contraceptives

28
Q

G Protein Coupled Receptors (GPCRs)

Describe the structural motif

A
  • Extracellular domain (EDC) : binds to signal
  • Tran Membrane (TM) domain: 7 alpha helices
  • Intracellular Domain (ICD): interacts with G proteins
29
Q

G Protein Coupled Receptors (GPCRs)

What is the order of GPCR signaling?

A

GPCR –> Trimeric G protein –> Effector enzyme –> 2nd messenger –> Targets of 2nd messenger –> Biological response

30
Q

G Protein Coupled Receptors (GPCRs)

Trimeric G proteins contain what subunits?

A

3!

Alpha, Beta, Gamma

31
Q

G Protein Coupled Receptors (GPCRs)

An inactive G protein has a _____ bound to it’s alpha subunit

A

GDP

32
Q

G Protein Coupled Receptors (GPCRs)

How does the G protein become active?

A

Exchange GDP for GTP

*USES GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF)

33
Q

G Protein Coupled Receptors (GPCRs)

What helps return the G protein to it’s inactive state?

A

GTPase-activating protein (GAP)

34
Q

What does Gs do?

A

Stimulates adenylate cyclase

35
Q

What does Gt do?

A

Stimulates cGMP phosphodiesterase

36
Q

What does Gi do?

A

Inhibits adenylate cyclase

37
Q

What does Gq do?

A

Activates phospholipase C

38
Q

Receptor Tyrosine Kinase (RTK)

Describe the structural motif of receptor tyrosine kinases

A
  • EDC contains signaling molecule binding site
  • Single helix that spans membrane
  • ICD that possesses tyrosine kinase activity
39
Q

Receptor Tyrosine Kinase (RTK)

Binding of ligand causes…

A

dimerization

40
Q

Receptor Tyrosine Kinase (RTK)

Dimerized receptor…

A

phosphorylates tyrosine residues

41
Q

Receptor Tyrosine Kinase (RTK)

Phospho-tyrosines are recognized by ______ and _____ which activate downstream signaling pathways

A

Adaptor; Docking proteins

*RAS dependent, RAS independent

42
Q

Receptor Tyrosine Kinase (RTK)

RAS-dependent signaling factilitated by ______ family

A

MAPK

43
Q

CORRELATION BOXES:

RAS and Cancer

A
  • Mutant forms of RAS (or it’s GEFs or GAPs) have been implicated in LOTS of cancers
  • Mutations decrease GTPase activity and lock it in active GTP bound state
44
Q

What G protein can Epinephrine bind to?

A

Gs or Gi

45
Q

What is the importance of Epinephrine with Gs?

A

Epi binds to BETA-ADRENERGIC RECEPTOR;

EPI is a nonselective agonist of all adrenergic receptors

46
Q

What G protein does Histamine bind to?

A

Gs

47
Q

What does Dopamine bind to?

A

Dopamine D2 receptor; Gi

48
Q

What binds to Gq?

A

Acetylcholine

49
Q

What does Acetylcholine bind to?

A

Muscarininc acetylcholine M3 receptor; Gq

50
Q

What happens when light hits rhodopsin (Gt)?

A

Vision

51
Q

What is Viagra?

A

Inhibitor of cGMP PDE;

increase concentration of cellular cGMP leading to smooth muscle relaxation and vasodilation

52
Q

What does NO do in relationship to smooth muscle relaxation?

A

NO diffuses to neighboring muscle and activated guanylate cyclase, leading to production of cGMP

cGMP produced from activated guanylate cyclase leading to smooth muscle relaxation and vasodilation.

53
Q

CORRELATION BOX:

Cholera toxin:

A

Prevents inactivation of Gprotein; TURNED ON!!!

  • Covalent modification of alpha subunits ADP ribosylation of Arg, decreases GTPase activity
  • G(s alpha) remains active and continuously stimulates ADENYLATE CYCLASE resulting in TOO MUCH cAMP

-Too much cAMP opens Cl- channels, loss of electrolytes and water –> Diarrhea

54
Q

CORRELATION BOX:

Pertussis (Whooping cough)

A

-G(i-alpha)

TOO MUCH cAMP

  • LESS INHIBITION of AC
  • Loss of fluids and excessive mucous in airway epithelial cells
55
Q

What is signal desensitization?

A

Ability to turn off or ignore a signal

56
Q

How can you induce SIGNAL DESENSITIZATION?

A
  • Receptor sequestration: endosome

- Receptor destruction: endosomes + lysosomes

57
Q

GRKs:

What are G protein Receptor Kinases?

A

GRKs phosphorylate the GPCR

Allows arrestin to bind to phosphorylated GPCR

RESULT: G-alpha-GDP does not get converted to Galpha-GTP, i.e. INACTIVATED G-PROTEIN complex

58
Q

RAS-dependent signaling facilitated by ________

A

MAPK

59
Q

RAS-independent signaling facilitated by ________

A

different kinase

60
Q

CORRELATION BOX:

RAS and Cancer

A

Mutant forms of RAS or it’s GEFs or GAPs have been implicated in wide range of human cancers

61
Q

CORRELATION BOX:

RTKs and Cancer

A

RTKs are the target of pharmacological inhibitors. Excessive signaling from mutated/overexpressed RTKs associated with cancer

HER2

MCM Exam 2 (13 decks)

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