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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
Q

How is signaling terminated in GPCR?

A
  • hydrolysis of GTP to GDP
  • occurs through the GTPase activity of the Ga subunit
  • Ga reunites with GBy, completing a cycle
26
Q

What does Gas do?

A

-stimulates adenylyl cyclase, causing increased cAMP formation

27
Q

What does Gai do?

A
  • inhibits AC, decreasing cAMP formation

- opens cardiac K+ channels decreasing heart rate

28
Q

What does Gao do?

A
  • limited effects of alpha subunit

- effectors not yet clear

29
Q

What does Gaq do?

A
  • activates PLC

- increases production of IP3, DAG, and cytoplasmic Ca2+

30
Q

What does GBy do?

A
  • same as for Ga subunits
  • also activate K+ channels
  • inhibit voltage-gated Ca2+ channels
  • activate GPCR kinases
  • activate mitogen-activated protein kinase cascade
31
Q

Which Ga subtype is activated by cholera toxin?

A
  • Gas

- blocks GPAse activity, thus preventing inactivation

32
Q

Which Ga subtypes is blocked by pertussis toxin?

A
  • Gai

- prevents dissocitation of GaBy complex

33
Q

How is specificity achieved with GPCRs?

A
  • molecular variation withing the Ga-subunit

- for example… Gas and Gai stimulate and inhibit the enzyme adenylyl cyclase

34
Q

What are the 4 targets for G-proteins?

A
  • Adenylyl Cyclase: cAMP
  • PLC: IP3, DAG, Ca2+
  • Ion channels CA2+ and K+
  • Thoa/Rho kinase: smooth muscle contraction, cell growth
35
Q

How is cAMP inactivated?

A

-hydrolysis to 5’-AMP by PDEs

36
Q

What does cAMP do?

A
  • activates Protein kinases… like PKA

- that goes on to phosphorylate stuff

37
Q

What is the substrate for the membrane bound enzyme PLC?

A
  • PIP2

- splits it into DAG and IP3

38
Q

Which G ptn activates PLC

A

Gq

39
Q

What does IP3 do?

A
  • goes to ER and activates Ca2+ channels
  • Ca2+ released into cytosol
  • Gets dephosphorylated and recycled to form PIP2
40
Q

What does DAG do?

A
  • activates membrane-bound PKC
  • that P’s a number of intracellular ptns
  • DAG is lipophilic and remains within the membrane
41
Q

Which G ptn will activate a channel after it dissociates from Gao?

A

the GBy part!

42
Q

How is Rho activation supported?

A
  • GEFs
  • they exchange the GDP for a GTP
  • inactivated by GAPs: GTPase-activating proteins… promote hydrolysis of GTP to GDP
43
Q

What are some of the end effects of Rho kinase receptor?

A

-smooth muscle contraction and proliferation, angiogenesis, and synaptic remodeling

44
Q

What are nuclear receptors bound by?

A

steroid hormones

-thyroid hormone is a steroid hormone

45
Q

What 3 domains do nuclear receptors have?

A
  • AF-1: activation function 1
  • DBD: DNA binding Domain
  • LBD: Ligand binding domain
46
Q

Which domain plays a role in dimerization?

A

DBD

  • highly conserved
  • binds region upstream from the target gene
47
Q

What is the thing within LBD that changes and allows recruitment of coazctivators or corepressors?

A

AF2: activating function 2

48
Q

What are the classic steroid nuclear receptors?

A
  • GR
  • MR
  • ER
  • PR
  • AR
49
Q

What are the orphan receptors?

A
  • those that bind to:
  • retinoids
  • thyroid hormone
  • Vit D
  • Xenobiotic
  • Androstane
  • Lipids
  • FA’s
50
Q

What is an example of a coactivator that would come with activation of a nuclear receptor?

A
  • histone acetylase

- makes Chromatin open up

51
Q

What is something that could be a corepressor?

A
  • histone deacetylase

- causes chromatin to become tightly packed… preventing transcriptional activation

52
Q

What are some common heterodimeric nuclear receptors?

A
  • RXR
  • RAR
  • probably the other ones we will run into are homodimers
53
Q

What is HRE

A

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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