lectures 10-12 Flashcards

1
Q

hydrophilic hormone steps

A
  1. bind PM receptors
  2. signal transduction pathways activated
  3. activate g-switch proteins/second messengers or tyrosine kinases
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2
Q

hydrophobic hormone steps

A
  1. diffuse through cell membrane
  2. activate cytosolic receptors, move to nucleus
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2
Q

effector protein

A

-usually last in signal pathway
-shuts off pathway

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2
Q

endocrine signalling

A

-epinephrine, insulin
-signal carried through blood vessels to target cell

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2
Q

paracrine signalling

A

-neurotransmitters, growth factors
-signal released to neighboring cells only

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3
Q

autocrine signalling

A

-growth factors
-cells respond to signals they produce

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4
Q

membrane protein signals

A

-direct cell to cell contact signalling

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5
Q

cAMP function

A

-secondary messenger from adenylyl cyclase by phosphodiesterase
-activates PKA

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6
Q

cGMP function

A

-secondary messenger from GTP by guanylyl cyclase
-activates PKG and cation channels

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7
Q

IP3/DAG function

A

-secondary messenger from PIP2 by phospholipase C
-open Ca2+ channels and activate PKC

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8
Q

water soluble secondary messengers

A

cAMP, cGMP

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9
Q

lipid soluble secondary messengers

A

IP3, DAG

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10
Q

kinase function

A

-phosphorylate proteins, activating them

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11
Q

phosphorylase function

A

-dephosphorylate proteins, deactivating them

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12
Q

protein kinase A activation

A

-Thr197 phosphorylated in activation loop
-promotes ATP and substrate binding

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13
Q

g-protein coupled receptors function

A

-activate g proteins
-GDP -> GTP

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14
Q

g-protein activity

A

-GTPase activity, hydrolyze GTP->GDP

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15
Q

liver/skeletal epinephrine function

A

increase glucose concentration for energy production

16
Q

adipose tissue epinephrine function

A

breakdown triglycerides for energy production

17
Q

cardiac muscle epinephrine function

A

increase heart rate, o2 and glucose to peripheral tissues

18
Q

smooth muscle cell relaxation epinephrine function

A

increase blood flow and o2 intake

19
Q

intestine epinephrine function

A

fluid secretion

20
Q

GPCR signal transduction pathways (4):

A
  1. membrane spanning helices
  2. heterotrimeric g protein cycling GTP->GDP
  3. effector protein
  4. protein desensitizing signal pathway
21
Q

structure of GPCR’s

A

-7 transmembrane alpha helices (H1-H7)
-n-term. outside, c-term. inside
-4 extracellular segments (E1-E4)
-4 cytosolic segments (C1-C4)

22
Q

activation of effector from GPCR steps

A
  1. ligand bind -> receptor conformational change
  2. activated receptor binds trimeric g protein
  3. GEF activity allows release of GDP from a unit
  4. GTP binds -> dissociation of units b/y
  5. GTP/Ga activates effector
  6. GTPase hydrolyzes GTP->GDP and effector turns off
23
Q

guanine exchange factor function

A

activated receptor dissociating GDP

24
Q

GTPase-accelerating protein

A

activated effector leading to hydrolysis of GTP->GDP

25
Q

CREB activation steps:

A
  1. receptor stimulation -> rise in cAMP
  2. cAMP activates PKA, translocates to nucleus
  3. PKA phosphorylates and activates CREB
  4. activated CREB joins CBP, binds CRE on promoter
  5. CREB binding allows gene transcription
26
Q

receptor tyrosine kinase ligand

A

-hydrophilic signalling molecules
-cause receptor dimerization

27
Q

RAS/MAP kinase pathway overview / main proteins

A

-receptors activtate GTPase switch protein (Ras)
-Grb2 and SOS recruited through SH3/SH2 domains

28
Q

guanine nucleotide exchange factors use and example

A

-SOS
-release GDP

29
Q

GTPase accelerating proteins use

A

-hydrolyze GTP->GDP

30
Q

RAS kinase pathway steps (4)

A
  1. SOS -> Ras
  2. Ras -> Raf
  3. Raf -> MEK
  4. MEK -> ERC
31
Q

Ras activation steps (4)

A
  1. ligand bind to RTK
  2. phosphotyrosine on RTK allows Grb2 SH2 to bind
  3. SH2 on Grb2 binds Pro on SOS
  4. SOS releases GDP, binds GTP
32
Q

SH2 domain function

A

-bind phosphorylated Tyrosine residues

33
Q

SH3 domain function

A

-bind Proline-rich domains and motifs

34
Q

14-3-3 dimer function

A

-bound to Raf phosphoserine’s and stabilize Raf

35
Q

Ras/MAP kinase pathway STEPS (5)

A
  1. RTK active -> Ras-GTP
  2. 14-3-3 released, Raf active
  3. Raf activates MEK
  4. MEK activates ERK
  5. ERK activates different proteins
36
Q

MAP kinase and c-fos txn steps

A
  1. MAPK activates p90, translocate to nucleus
  2. p90 phosphorylate SFR
  3. MAPK translocate to nucleus, phosphoorylate TCF on c-fos gene
  4. c-fos transcribed
37
Q

phosphoinositide signaling pathway (PI-3) steps:

A
  1. RTK activate PI-3 kinase
  2. PI-3-phosphates formed which bind PH domains
  3. protein kinase B activated
38
Q

active protein kinase B function

A

-inactivate pro-apoptotic proteins
-synthesis of pro-apoptotic proteins

39
Q

PI-3 kinase products (3)

A
  1. phosphonositol 3,4-biphosphate (IP2)
  2. phosphonositol 4,5-biphosphate (IP2)
  3. phosphonositol 3,4,5-triphosphate (IP3)
40
Q

PH domain of PKB function

A
  1. bind PI2
  2. relocate PKB to plasma membrane
41
Q

PKB activation steps ():

A
  1. hormone binds, activated PI-3 kinase and PI-3 phosphates formed
  2. PI-3 binds PH domains of PKB and PDK2 to partially activate
  3. PDK1 phosphorylates Serines in PKB, fully activated