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Endo > Hormones and cell signalling 2 > Flashcards

Hormones and cell signalling 2 Flashcards

1
Q

List water soluble hormones

A
  • Serotonin
  • Melatonin
  • Histamine
  • Adrenaline
  • Noradrenaline
  • Thyroid stimualting hormone
  • Human growth hormone
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2
Q

What hormones exclusively use the adenyl cyclase signal transduction pathway?

A
  • ACTH
  • Calcitonin
  • FSH
  • Glucagon
  • LH
  • Prostaglandins
  • PH
  • Somatostatin
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3
Q

What hormones exclusively use the phospholipase C signal transduction pathway?

A
  • GnRH

- RH

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4
Q

What hormones exclusively use the tyrosine kinase signal transduction pathway?

A
  • Angiotensin II
  • EPO
  • GH
  • IGF-I
  • Insulin
  • Prolactin
  • Growth factors
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5
Q

What hormones exclusively use the guanylyl cyclase (cGM) signal transduction pathway?

A
  • ANP
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6
Q

List lipid soluble hormones

A
  • Steroid hormones
  • Thyroid hormones
  • Retinoids
  • Vitamin D
  • Cortisol
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7
Q

Describe receptor tyrosine kinases

A
  • Most abundant group of enzyme linked cell surface receptors
  • Intracellular domain has multiple tyrosine residues that can be altered by phosphoryation
  • Varying extracellular domains to discriminate between signalling molecules
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8
Q

Describe signalling via receptor tyrosine kinases

A
  • 2 ligands bind to 2 adjacent receptor chains, form dimer
  • Activates intracellular tyrosine kinase domain
  • Activated kinase domain transfers phosphate group from ATP to selected tyrosine side chains on receptor and subsequent signalling proteins that bind to phosphorylated receptors
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9
Q

List signalling molecules that act via receptor tyrosine kinases

A
  • Epidermal growth factor
  • Insulin
  • Insulin-like growth factors
  • Nerve growth factor
  • Platelet-derived growth pactors
  • Macrophage-colony-stimulating factirs
  • Fibroblast growth factors
  • Vascular endothelial growth factor
  • Ephrine (A and B types)
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10
Q

Outline how signals can be integrated

A
  • Different receptors bind different ligands
  • Have different intracellular effects
  • Converge at certain points, e.g. may both activate phospholipase C pathways
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11
Q

What is MAPK?

A

Mitogen activated protein kinase

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12
Q

How is Ras regulated?

A
  • Inactive when bound to GDP
  • Active when boudn to GTP
  • Carried out by GEF (guanine exchange factor)
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13
Q

Describe how Ras is activated by hormones

A
  • Hormone binds to receptor tyrosine kinase, dimerisation occurs
  • Autophosphorylation of tyrosines
  • Grb-2 binds
  • Regulates Ras GEF
  • Actigvated, swaps GDP on Ras for GTP
  • Activates Ras
  • Ras transmits signal
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14
Q

How can Ras lead to different responses to hormonal stimuli?

A
  • Different types of Ras

- Different degrees of Ras expression in cells

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15
Q

What signalling pathways are utilised by insulin and IGF?

A

MAPK and PI3K

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16
Q

What is the role of the MAPK pathway?

A

Regulates cell growth (cell division and protein synthesis)

17
Q

Outline the MAPK pathway

A
  • Ras activated
  • Activates MAP kinase kinase kinase (MAPKKK, aka Raf)
  • This phosphorylates (activates) MAP kinase kinase (MAPKK) called Mek
  • This phosphorylates (activates) MAP kinase (MAPK) called Erk
  • Erk phosphorylates (activates) target proteins (transcription factors)
18
Q

What is MAPK/Erk signalling cascade activated by?

A
  • Wide variety of receptors involved in growth and differentiation
    e. g. RTKs, integrins, ion channels
19
Q

What is the role of the PI3-kinase pathway?

A

Regulates cell growth and survival (inhibition of apoptosis)

20
Q

Describe the PI3-kinase pathway

A
  • Activated by binding of insulin to RTK
  • Activates (phosphorylates) protein kinase B (Akt)
  • Akt phosphorylates mTOR (kinase) which stimulates proliferation
  • Akt phosphorylates factors of Bcl-2 family which inhibits apoptosis
21
Q

Describe the role of MAPK insulin activity

A

Through MAPK pathway: insulin promotes cell growth and inhibits gluconeogenesis

22
Q

Describe the role ofthe PI3K pathway in insulin activity

A
  • Through PI3K pathways insulin:
  • Inhibits gluconeogenesis and glycogenolysis
  • Induces translocation of glucose transporter (GLUT-4) to membrane (more uptake)
  • Stimulates AA uptake and protein syntehsis
  • Stimulates lipid synthesis and inhibits lipolysis
23
Q

How is the phorphorylation cascade regulated in insulin signalling?

A

At each stage have protein phosphatases that inactivate that kinases produced at each step in order to downregulate

24
Q

How is insulin resistance linked to receptor tyrosine kinases?

A
  • IR may be due to loss of receptors

- May be due to loss of relay proteins (Ras)

25
Q

Outline the receptor tyrosine kinase in relation to oncology

A
  • Overstimualtion leads to cell growht and proliferation
  • Inhibition of apoptosis
  • Loss of control of growth and so tumours form
26
Q

What is the role of effector proteins in intracellular signalling?

A
  • Stimulated/activated by the signal transduction pathways
  • Translocate to nucleus
  • Modulate gene expression
  • Modulate gene expression by binding of effector protein to “signal response element” on gene promoters

Endo (30 decks)

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