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Endocrine II midterm > Kruse DSA: Endocrine Receptors and Signaling Pathways > Flashcards

Kruse DSA: Endocrine Receptors and Signaling Pathways Flashcards

1
Q

Where does the term hormone come from?

A

Greek: “to set in motion”

-useless but interesting

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2
Q

What binds its receptor with more affinity, T3 or T4?

A

T3

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3
Q

What are the 4 major types of receptors in the body?

A
  • ligand-gated ion channels
  • GPCRs
  • Kinase-linked receptors
  • Nuclear receptors
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4
Q

What hormones will get the Galpha(s) receptor?

A
  • B-adrenergic
  • LH, FSH, TSH
  • Glucagon
  • PTH
  • ACTH
  • GHRH, CRH
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5
Q

What does Gas receptor do?

A

-stimulates cAMP

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6
Q

What hormones get the Gi receptor?

A
  • alpha adrenergic

- Somatostatin

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7
Q

What does Gi do?

A
  • inhibition of cAMP production

- Activation of K+, Ca2+ channels

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8
Q

Which hormone will bind to RTKs?

A

-insulin

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9
Q

What does the RTK IRS-1 to IRS-4 do?

A

-MAP kinases, PI 3-kinase, RSK

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10
Q

What hormones get the cytokine receptor-linked kinase like JAK and other tyrosine kinases?

A
  • GH

- PRL

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11
Q

What does JAK do?

A
  • STAT
  • MAP kinase
  • PI 3-kinase,
  • IRS1
  • IRS2
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12
Q

What hormone gets the Serine Kinase?

A

-TGF-B

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13
Q

What signaling pathway does the serine kinase receptor activate?

A

Smads

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14
Q

At what level are the effects of kinase-linked receptors exerted?

A
  • gene transcription
  • GPCRs are really the only ones that just modulate intracellular signaling events… all the rest regulate gene transcription somehow
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15
Q

What gets the RTK again?

A

insulin

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16
Q

What kind of receptor does TGF-B bind onto?

A
  • Serine/threonine kinase receptor

- same as RTK but not with tyrosine

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17
Q

Which kinase-linked reeceptors lack intrinsic enzyme activity?

A

cytokine receptors

  • they just activate cytosolic kinases
  • examples include receptors for GH and PRL
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18
Q

What two things will bind to cytokine receptors again?

A

-GH and PRL

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19
Q

What happens to a kinase-linked receptor when the ligand binds it?

A

dimerization

-the end result is activation or inhibition of TF’s via phosphorylation

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20
Q

In a GPCR, where is the N and C terminals

A
  • N is extracellular

- C is intracellular

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21
Q

What does the a subunit of GPCR do?

A
  • binds to guanine nucleotides, activates effector ptns when bound to GTP, has enzymatic activity
  • catalyzes the conversion of GTP to GDP resultin in a-subunit inactivation
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22
Q

What do the B and gamma subunits of GPCR do?

A
  • they form a dimer and remain together
  • membrane localization of G ptn and directs signaling such as activation of ion channels and binding sites for G ptn receptor kinases
23
Q

What does the GPCR look like when it’s not activated?

A
  • unattached GaBy trimer associated with the cytoplasmic side of the membrane
  • GDP bound to the alpha subunit
24
Q

What happens when the GPCR is activated?

A
  • conformational change in cytoplasmic domain of receptor
  • cause it to have high affinity for the GaBy
  • GDP dissociates from alpha
  • replaced by GTP
  • trimer dissociates
25
How is signaling terminated in GPCR?
- hydrolysis of GTP to GDP - occurs through the GTPase activity of the Ga subunit - Ga reunites with GBy, completing a cycle
26
What does Gas do?
-stimulates adenylyl cyclase, causing increased cAMP formation
27
What does Gai do?
- inhibits AC, decreasing cAMP formation | - opens cardiac K+ channels decreasing heart rate
28
What does Gao do?
- limited effects of alpha subunit | - effectors not yet clear
29
What does Gaq do?
- activates PLC | - increases production of IP3, DAG, and cytoplasmic Ca2+
30
What does GBy do?
- same as for Ga subunits - also activate K+ channels - inhibit voltage-gated Ca2+ channels - activate GPCR kinases - activate mitogen-activated protein kinase cascade
31
Which Ga subtype is activated by cholera toxin?
- Gas | - blocks GPAse activity, thus preventing inactivation
32
Which Ga subtypes is blocked by pertussis toxin?
- Gai | - prevents dissocitation of GaBy complex
33
How is specificity achieved with GPCRs?
- molecular variation withing the Ga-subunit | - for example... Gas and Gai stimulate and inhibit the enzyme adenylyl cyclase
34
What are the 4 targets for G-proteins?
- Adenylyl Cyclase: cAMP - PLC: IP3, DAG, Ca2+ - Ion channels CA2+ and K+ - Thoa/Rho kinase: smooth muscle contraction, cell growth
35
How is cAMP inactivated?
-hydrolysis to 5'-AMP by PDEs
36
What does cAMP do?
- activates Protein kinases... like PKA | - that goes on to phosphorylate stuff
37
What is the substrate for the membrane bound enzyme PLC?
- PIP2 | - splits it into DAG and IP3
38
Which G ptn activates PLC
Gq
39
What does IP3 do?
- goes to ER and activates Ca2+ channels - Ca2+ released into cytosol - Gets dephosphorylated and recycled to form PIP2
40
What does DAG do?
- activates membrane-bound PKC - that P's a number of intracellular ptns - DAG is lipophilic and remains within the membrane
41
Which G ptn will activate a channel after it dissociates from Gao?
the GBy part!
42
How is Rho activation supported?
- GEFs - they exchange the GDP for a GTP - inactivated by GAPs: GTPase-activating proteins... promote hydrolysis of GTP to GDP
43
What are some of the end effects of Rho kinase receptor?
-smooth muscle contraction and proliferation, angiogenesis, and synaptic remodeling
44
What are nuclear receptors bound by?
steroid hormones | -thyroid hormone is a steroid hormone
45
What 3 domains do nuclear receptors have?
- AF-1: activation function 1 - DBD: DNA binding Domain - LBD: Ligand binding domain
46
Which domain plays a role in dimerization?
DBD - highly conserved - binds region upstream from the target gene
47
What is the thing within LBD that changes and allows recruitment of coazctivators or corepressors?
AF2: activating function 2
48
What are the classic steroid nuclear receptors?
- GR - MR - ER - PR - AR
49
What are the orphan receptors?
- those that bind to: - retinoids - thyroid hormone - Vit D - Xenobiotic - Androstane - Lipids - FA's
50
What is an example of a coactivator that would come with activation of a nuclear receptor?
- histone acetylase | - makes Chromatin open up
51
What is something that could be a corepressor?
- histone deacetylase | - causes chromatin to become tightly packed... preventing transcriptional activation
52
What are some common heterodimeric nuclear receptors?
- RXR - RAR - probably the other ones we will run into are homodimers
53
What is HRE
hormone response element - the part of the DNA that is bound by the Nuclear receptor - the gene is downstream

Endocrine II midterm (13 decks)

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