lecture 2 Flashcards

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1
Q

describe timing of cell proliferation

A

occurs at same time across embryo

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2
Q

what does intracellular signaling do to cell proliferation

A

controls/synchronizes mechanism across 10k+ cells across embryo

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3
Q

describe regulation of cell proliferation

A

tightly regulatedw

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4
Q

what do signaling pathways do for cell prolfieration

A

control when, where, how cell division occurs

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5
Q

what happens if pathway in cell that tells cell now isn’t the time to divide is mutated

A

cell is not prevented from dividing, cancer happens

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6
Q

describe cancer

A

DNA in cells become mutated, proteins that control when cell divides or not aren’t active, cells are dividing when they shouldn’t

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7
Q

what happens when pathways regulating cell movement are mutated

A

metastasis; tumor metastasizes across the body

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8
Q

basically what regulates cell division

A

signaling

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9
Q

what is human fibroblast

A

maintains tissue homeostasis

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10
Q

what does fibroblast need to do

A

signals in env. to tell it what to do; awaits signals to be activated

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11
Q

PDGF

A

platelet derived growth factor

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12
Q

how is PDGF introduced

A

secreted in extracellular environment; diffuses till it reaches fibroblast

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13
Q

what happens when PDGF reaches fibrobalst

A

binds to receptor in plasma membrane

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14
Q

what does this binding event cause

A

chem rxn inside of cell that triggers mechanism of cell proliferation

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15
Q

what is every step of this mechanism controlled by

A

intracellular signaling

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16
Q

what is example of extracellular signal molecule

A

PDFG

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17
Q

what is plasma membrane generally

A

barrier to transmission of info from outside to inside of cell

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18
Q

what is plasma membrane insoluble to

A

water insoluble

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19
Q

what is PDGF soluble to

A

water soluble (hydrophilic)

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20
Q

where is PDGF secreted

A

into extracellular environment so it can diffuse till it reaches target

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21
Q

what does this mean for PDGF in membrane

A

can diffuse but can’t pass thru plasma membrane

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22
Q

what is needed for signaling molecules to pass thru

A

receptor protein/plasma receptor

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23
Q

key property of receptor protein?

A

spans the plasma membrane; part of it is on outside, part is anchored in lipid bilayer, part is inside cell

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24
Q

what happens when growth factor binds receptor

A

triggers conformational change in receptor protein,

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25
Q

what does this binding activate

A

signaling pathways on cytoplasmic side (inside) of plasma membrane

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26
Q

what does the conformational change do

A

switches it from off state/inactive to active

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27
Q

what happens when any protein becomes active

A

it’s able to bind its downstream targets and activate them

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28
Q

what’s at the end of the pathway

A

effector proteins

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29
Q

what happens to effector proteins as signals are transmitted

A

they get farther and farther from plasma membrane

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30
Q

4 types of extracellular signals/ligands

A

paracrine signaling, endocrine signaling, synaptic signaling, contact-dependent

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31
Q

paracrine signaling

A

signaling ligand is secreted but never enters bloodstream, just interstitial [short range]

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32
Q

example of paracrine signaling

A

PGDF

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33
Q

endocrine signaling

A

signaling ligand travels through bloodstream [long distance]

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34
Q

example of endocrine signaling

A

hormones

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35
Q

contact dependent signaling

A

ligand is expressed on surface of cell (outside environmnent), not released; cell-cell contact dependent

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36
Q

what happens in contact-dependent signaling

A

when target cells bind ligand, requires contact of two cells

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37
Q

synaptic signaling

A

neurotransmitter

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38
Q

what receptors do signal molecules bind to

A

cell-surface receptors or intracellular receptors

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39
Q

what types of signaling do these receptors apply to

A

contact dependent and paracrine signaling

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40
Q

describe signaling molecule of cell surface receptors

A

hydrophilic; can’t enter membrane, that’s why you need cell-surface receptor that spans whole membrane

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41
Q

describe signaling molecule of intracellular receptors

A

small, hydrophobic

42
Q

why is hydrophobic molecule a problem

A

once secreted they have trouble navigating through blood; need carrier protein that’s water soluble

43
Q

what do we deal with most of the time

A

receptors at surface of plasma membrane

44
Q

example of same ligand triggering different effects depending on cell

A

acetylcholine

45
Q

what effect does acetylcholine have on heart pacemaker cell

A

decreased rate of firing

46
Q

what effect does acetylcholine have on salivary gland cell

A

secretion

47
Q

what effect does acetylcholine have on skeletal muscle cell

A

contraction

48
Q

what does acetylcholine do

A

binds to G protein coupled receptor (specific class of receptor)

49
Q

describe GPCR

A

huge, passes plasma membrane 7 times

50
Q

what does acetylcholine do in heart pacemaker cell

A

acetylcholine ligand binds to receptor, triggers change in frequency of firing pacemaker cell, slowing heart beat

51
Q

what does acetylcholine do in salivary gland cell

A

binds to receptor, triggers component in rate of secretion of saliva

52
Q

why does acetylcholine does diff stuff in cell

A

these cells don’t express same types of pathways

53
Q

three major classes of cell-surface receptor proteins

A

ion-channel coupled, G-protein coupled, enzyme-coupled receptors

54
Q

GPCR

A

pass membrane 7 times, when inactive, held together in heterotrimeric complex

55
Q

enzyme-coupled receptors

A

always receptor tyrosine kinases

56
Q

ion-channel coupled

A

flow of neurons from inside to outside of cells

57
Q

how do cell-surface receptors relay signals

A

thru intracellular signaling molecules

58
Q

phosphorylation is

A

post-translational modifications

59
Q

what can phosphorylation control

A

protein activity, intracellular signaling; basically a way for proteins to control their activity

60
Q

describe phosphorylation

A

signal comes in, activates receptor, activates kinase associated w/ it

61
Q

what happens when kinase is activated

A

binds to downstream target, grabs floating ATP, plucks a phosphate group, covalently binds to downstream target

62
Q

what does it mean if there’s a way to activate signaling pathway

A

there’s a way to inactivate signaling pathway

63
Q

if cells can’t regulate (turn on or off), what happens

A

bad shit

64
Q

what turns off the pathway in phosphorylation

A

second enzyme (phosphatases)

65
Q

job of phosphatases

A

to hydrolyze the phosphate bond to proteins and release it

66
Q

what does kinase do

A

adds phosphate to activate it

67
Q

what does phosphatase do

A

removes phosphate; everything gets returned

68
Q

what’s another nucleotide that controls intracellular signaling

A

GTP

69
Q

what happens when protein bound to GDP form

A

(2 phosphates); inactive

70
Q

what happens to activate receptor

A

signal comes in, GDP kicked off into cytoplasm (released), G protein is gonna bind to next guanine nucleotide it bumps into (GTP)

71
Q

what does GTP binding do

A

triggers conformational change within G protein that allows it to bind to next target

72
Q

GDP version

A

off

73
Q

GTP version

A

on

74
Q

what are G proteins always bound to

A

nucleotide

75
Q

what happens in GTP hydrolysis

A

P leaves, GDP remains, turns it off

76
Q

what happens when G protein turned on

A

GDP is released (kicked off), new molecule of GTP binds in its place [activated]

77
Q

what happens to turn G protein off

A

GTP remains bound, just converted in GDO and hydrolyzed; phosphate leaves

78
Q

GEF

A

enzyme; guanine exhcange factor

79
Q

what does GEF control

A

removal of GDP and its replacement by GTP; protein that activates pathways

80
Q

what does GEF do

A

binds onto inactive G protein and removes GDP and replaces it w/ GTP

81
Q

what would happen if no GEF

A

would never become activated

82
Q

what are G proteins known as

A

GTPase

83
Q

what can GTPase do

A

self timer to turn itself off, but it’s slow

84
Q

why dow e need second regulator protein to turn it off

A

inactivating GAP protein will bind to GTPase, accelerates timer

85
Q

what are GAPs

A

GTPase Activating Protein

86
Q

what is being activated in GAPs

A

intrinsic GTPase activity (so it can turn itself off quicker)

87
Q

how can multiple proteins find each other in hella crowded env.? and quickly?

A

proteins pre-positioned at right place by scaffold proteins so they are where they need to be at the right time

88
Q

describe scaffolding in receptor tyrosine kinases

A

receptor acts as scaffold; when RTKs phosphorylate each other, creates scaffold or docking sites where

89
Q

what does scaffolding require

A

specific protein domains to mediate

90
Q

positive feedback

A

when B is activated, it binds and activates more copies of A

91
Q

what DONT you need when B is activated

A

initial signal molecule

92
Q

negative feedback

A

A activates B signaling protein, B binds and inhibits A

93
Q

what happens when pathway turns on

A

tries to turn itself back off

94
Q

pos feedback in kinase

A

when upstream signal kinase is activated, binds and phosphorylates substrate E (inactive kinase); goes and feedbacks on earlier step on pathway

95
Q

what happens as long as signal is present in pos

A

pathway is activated

96
Q

what happens if signal is gone in pos

A

pathway still on; but need initial molecule at some point

97
Q

what happens when kinase E is activated thru phosphorylation thru upstream kinase

A

phosphorylates an inhibitor that deactivates E

98
Q

how do cells adjust sensitivity to a signal

A

negative feedback (turns itself off), receptor inactivation (G proteins and natty timer)

99
Q

how are cell dynamics controlled

A

intracellular signaling

100
Q

how do receptors work

A

receive signal, transmit it into cell thru signal transduction pathways

101
Q

what governs signal transmission + effects

A

proteins and post-translational modification

102
Q

how are signals modulated

A

pos and neg feedback; inhibited