hormone signaling pathways

Question 1

what is an example of endocrine signaling

Answer 1

epinephrine

Question 2

what is an example of paracrine signaling

Answer 2

testosterone

Question 3

receptors involved in hydrophilic hormone signaling

Answer 3

GPCRs and RTKs

Question 4

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

Answer 4

HSP90, HSP90. hormone response element (HRE)

Question 5

nuclear receptors

Answer 5

already present in nucleus bound to DNA

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

Question 6

hydrophilic signal molecules: aa derived

Answer 6

melatonin, epinerphrine, norepinephrine, dopamine, histamine, serotonin

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Question 7

hydrophilic signal molecules from lipid metabolsim

Answer 7

acetylcholine

Question 8

hydrophilic signal molecules: polypeptides

Answer 8

TSH, cytokines, insulin, glucagon

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Question 9

what is the second messenger for epinephrine

Answer 9

GPCR

Question 10

what kind of receptor is insulin

Answer 10

receptor tyrosine kinase

Question 11

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

Answer 11

hydrophilic has short, lipophilic has long

Question 12

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

Answer 12

GEF and on alpha subunit of G protein

Question 13

how does the G protein go back to inactive GDP form

Answer 13

has intrinsic GTPase activity which is accelerated by GAP

Question 14

what does Gs stimulate

Answer 14

adenylate cyclase and increase in cAMP and activation of PKA

Question 15

what does Gt stimulate

Answer 15

hydrolysis of cGMP by cGMP PDE triggered by light in vision

Question 16

what does Gi do

Answer 16

inhibits adenylate cyclase so no cAMP and no PKA

Question 17

how is PKA activated

Answer 17

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

Question 18

how is cAMP turned off

and what inhibits this enzyme

Answer 18

it is hydrolyzed into AMP by phosphodiesterase (PDE)

-caffeine inhibits this

Question 19

Gq signaling steps

Answer 19

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

Question 20

epinephrine binds to what type of GPCR protein

Answer 20

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

Question 21

what effects does epinephrine have on broncial and intestinal smooth muscle

Answer 21

relaxation

Question 22

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

Answer 22

Gi and constriction of SM

Question 23

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

Answer 23

Gs and relaxes bronchiole and intest smooth muslce

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

Question 24

histamine binds ___ receptor coupled with ___ G protein

-effect?

Answer 24

H2, and Gs

-bronchoconstriction and allergic rxns

Question 25

a1 adrenergic receptor is linked to what G protein

Answer 25

Gq

Question 26

epinephrine and CREB

Answer 26

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

Question 27

how is inactive insulin stored in body

Answer 27

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

Question 28

the active form of insulin is a __

Answer 28

monomer

Question 29

regulation of insulin secretion

Answer 29

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

Question 30

insulin signaling RAS dependent pathway

Answer 30

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

Question 31

insulin signaling RAS-independent pathway

Answer 31

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)

Question 32

insulin resistance

Answer 32

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

Question 33

what are Ser/Thr kinases activated by

Answer 33

cytokines, free FA, DAG, inflammatory molecules

Question 34

3 domains of nuclear receptors

Answer 34

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

Question 35

ligand binding domain is bound by what

Answer 35

inhibitory proteins while inactive | -ligand binding releases this

Question 36

2 responses of steroid hormones

Answer 36

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

Question 37

where is ERa expressed

Answer 37

``` in female reproductive tract mammary gland hypothalamus endotelial cells vascular SM ```

Question 38

where is ER-beta expressed

Answer 38

prostate and ovaries

Question 39

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

Answer 39

ERa

Question 40

how does tamoxifen work

Answer 40

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

Question 41

molecular mechanism of action of estrogen receptor

Answer 41

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

Question 42

some evidence that estrogen receptor is located where?

Answer 42

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