hormone signaling pathways Flashcards

1
Q

what is an example of endocrine signaling

A

epinephrine

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2
Q

what is an example of paracrine signaling

A

testosterone

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3
Q

receptors involved in hydrophilic hormone signaling

A

GPCRs and RTKs

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4
Q

cytoplasmic receptors exists in an inactive complex with ___ and upon binding to hormone ___ dissociates. The hormone receptor complex goes to the nucleus and binds the __ ___ ___ in promoter region of specific genes

A

HSP90, HSP90. hormone response element (HRE)

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5
Q

nuclear receptors

A

already present in nucleus bound to DNA

-hormone signal activates the complex and allows for interactions with additional proteins

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6
Q

hydrophilic signal molecules: aa derived

A

melatonin, epinerphrine, norepinephrine, dopamine, histamine, serotonin

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7
Q

hydrophilic signal molecules from lipid metabolsim

A

acetylcholine

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8
Q

hydrophilic signal molecules: polypeptides

A

TSH, cytokines, insulin, glucagon

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9
Q

what is the second messenger for epinephrine

A

GPCR

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10
Q

what kind of receptor is insulin

A

receptor tyrosine kinase

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11
Q

hydrophilic meds vs lipophilic meds, which has a long half life, which has short

A

hydrophilic has short, lipophilic has long

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12
Q

what exchanges GDP for GTP and what subunit of g protein does this occur on

A

GEF and on alpha subunit of G protein

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13
Q

how does the G protein go back to inactive GDP form

A

has intrinsic GTPase activity which is accelerated by GAP

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14
Q

what does Gs stimulate

A

adenylate cyclase and increase in cAMP and activation of PKA

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15
Q

what does Gt stimulate

A

hydrolysis of cGMP by cGMP PDE triggered by light in vision

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16
Q

what does Gi do

A

inhibits adenylate cyclase so no cAMP and no PKA

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17
Q

how is PKA activated

A

PKA has 2 Regulatory subunits and 2 catalyic subunits

  • when cAMP binds to regulatory subunits it causes the complex to dissociate
  • free catalytic subunits phosphorylate target proteins
18
Q

how is cAMP turned off

and what inhibits this enzyme

A

it is hydrolyzed into AMP by phosphodiesterase (PDE)

-caffeine inhibits this

19
Q

Gq signaling steps

A

1) signal binds, GDP swapped for GTP on alpha subunit
2) a-GTP activates PLC to convert PIP2 to IP3 and DAG
3) IP3 binds and releases Ca2+ stores from SR
4) increased intracellular Ca2+ causes PKC to go to plasma membrane where it is activated by DAG and phosphorylates target proteins
5) calcium also binds calmodulin which activates myosin light chain kinase and CaM kinase
6) MLC kinase phosphorylates myosin light chains and causes smooth muscle contraction
- CaM kinase phosphorlyates target proteins to alter activities

20
Q

epinephrine binds to what type of GPCR protein

A

all adrenergic receptors: a1,a2,B1,B2,B3

21
Q

what effects does epinephrine have on broncial and intestinal smooth muscle

A

relaxation

22
Q

epinephrine binding alpha2 adrenergic receptor is associated with what G protein and what effect

A

Gi and constriction of SM

23
Q

epinephrine binding to B adrenergic receptor is associated with what G protein

A

Gs and relaxes bronchiole and intest smooth muslce

  • increases glycogen and TG breakdown
  • increases glycolysis in musle
  • causes contraction of heart
24
Q

histamine binds ___ receptor coupled with ___ G protein

-effect?

A

H2, and Gs

-bronchoconstriction and allergic rxns

25
Q

a1 adrenergic receptor is linked to what G protein

A

Gq

26
Q

epinephrine and CREB

A

epinephrine binds to B Gs receptor eventually leads to activation of PKA which phosphorylates CREB
-CREB-P goes to nucleues and binds CRE which activates gene expression

27
Q

how is inactive insulin stored in body

A

as a hexamer with zinc in center connected to polypeptide via histadine

28
Q

the active form of insulin is a __

A

monomer

29
Q

regulation of insulin secretion

A

glucose comes in through GLUT then phosphorylated by glucokinase

  • participates in glycolysis and enters TCA which makes ATP and shuts of K+ ATPase
  • causes depolarization of membrane so Ca2+ comes in
  • calcium causes fusion of granules to membrane and release into the bloodstream
30
Q

insulin signaling RAS dependent pathway

A

1) insulin binds alpha subunit, RTK phosphorylates itself and B subunit
2) this recruits IRS-1 which then gets phosphorylated by RTK
3) GRB-2 binds phosphorylated IRS-1
4) this activates RAS then MAP kinase
5) leads to increased txn of glucokinase
6) increases glucose uptake and glycogen synthesis

31
Q

insulin signaling RAS-independent pathway

A

1) insulin binds alpha subunit, RTK phosphorylates itself and B subunits
2) IRS-1 recruited and phosphorylated
3) P13 kinase binds phophorylated IRS-1
4) PI3-kinase activates phosphorylates phosphoinositides to make PIP3
5) PIP3 stimulates recritment of PKB to membrane and activates it
6) eventually leads to increased GLUT4 to PM;
7) actiavtion of glycogen synthase (inhibits glycgoen synthase kinase)

32
Q

insulin resistance

A

increased phophorlyation of serine via ser/thr kinase instead of tyrosine in the insulin receptor and IRS
-this inactivates IRS1 and 2 leading to degradation

33
Q

what are Ser/Thr kinases activated by

A

cytokines, free FA, DAG, inflammatory molecules

34
Q

3 domains of nuclear receptors

A

DNA binding domain (highly conserved)
Ligand binding domain
Activation Function 1 domain

35
Q

ligand binding domain is bound by what

A

inhibitory proteins while inactive

-ligand binding releases this

36
Q

2 responses of steroid hormones

A

primary early response

- primary protein then shuts off early primary response and also turns on secondary response genes

37
Q

where is ERa expressed

A
in female reproductive tract
mammary gland
hypothalamus
endotelial cells
vascular SM
38
Q

where is ER-beta expressed

A

prostate and ovaries

39
Q

both Er-a and Er-b are expressed in breast cancers but ___ is predominant form responsible for growth regulation

A

ERa

40
Q

how does tamoxifen work

A

its a drug metabolized by cytochrome p450 then turns to 4-hydroxy-tamoxifen
-this raises affinity by 40X
binds receptor tight, recruits histone deacetylase 1
-stabilize nucleosome structure and prevent interaction with GTA

41
Q

molecular mechanism of action of estrogen receptor

A

agonist binds which recruit co-activator proteins to modify chromatin structure and activate HAT
-this leads to recruitment of GTA and induces txn of proliferation

42
Q

some evidence that estrogen receptor is located where?

A

in the cytosol, estrogen binding causes dimerization and translocation to the nuclues