Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

bio 211 > lecture 4 > Flashcards

lecture 4 Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

example of enzyme coupled receptors

A

PDGF; paracrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is PDGF molecule structure-wise

A

dimer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what does PDGF indicate

A

there’s a wound near by

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is PDGF

A

a ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are RTKs always activated by

A

ligand dimer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are inactive receptors (structure-wise)

A

monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the one exception to enzymes activated by ligand dimers

A

EGF (epithelial growth factor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe EGF

A

signaling molecule isn’t a dimer but still dimerizes receptor complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

describe inactive RTK

A

enzymatic and kinase activity is off

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what happens when ligand binds RTk

A

binds to 2 RTKs (cuz its a dimer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what does binding do

A

brings the inactive receptors in close proximity, initiates kinase activity –> trans autophosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what kind of activation in PDGF

A

dimerized induced activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how are RTKs diff from GPCRs in terms of ligands

A

RTKs have restricted subset of ligands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are major class of signaling ligands that bind and activate RTKs

A

gowth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what kind of receptors are growth factors

A

paracrine receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what kind of receptor is Eph receptor

A

contact-dependent signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

who has more variety in structure RTK or GPCR

A

RTK s have more variety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

basically how are RTKs activated

A

2 tyrosine kinase domains are brought together when receptor binds to its dimerized ligand, becomes active, phosphorylate each other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is initiating step in transmitting signal across plasma membrane

A

dimerization of receptor in response to ligand binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is stage 1 kinda

A

PDGF binds, brings inactivated receptors close together, triggers minor conformational change in receptor (activates intrinsic kinase activity at low level)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how much kinase activity is activated

A

just enough that RTK can phosphorylate its neighbor at one position (single phosphorylation on cytoplasmic tails)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what triggers enhancement of kinase activity (step 2)

A

the single phosphorylation on tail

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is step 2 kinda

A

much more phosphorylation events happening; both receptors phosphorylated at multiple sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what does this phosphorylation create

A

hella scaffolding domains that allow other signaling molecules to bind to receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what does allowing other signaling molecules to bind to receptor do

A

allows them to be at right place at right time to transmit signals deeper and deeper into cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is another thing that allows them to transmit signals

A

they themselves become activated upon binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what does dimerization lead to

A

conformational change which leads to low level activity that does one phosphorylation event on either receptor; that elevates kinase activity even farther, then you get all this phosphorylation going on to bring in more signaling proteins that are activated to relay signal downstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

overall describe autophosphorylation

A

one phosphorylates the other, both serve as docking sites for downstream signaling proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is exception to the rule

A

EGF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how is EGF an exception

A

ligand isn’t dimerized; still it binds and brings together 2 components of EGF receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

describe EGF receptor

A

not symmetrical; 2 subunit receptors behave differently

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what are the EGF receptor

A

one is activator other is receiver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what happens when ligand binds activator

A

triggers conformational change that activates kinase activity of receiver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what does EGF receptor receiver do

A

phosphorylates itself on long flexible tail, and tail of activator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what is end result of EGF

A

same; dimerized receptor w/ multiple tyrosine phosphorylations to provide docking sites for signaling molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

why is EGF a rare case

A

only one member of receptor dimer is responsible for phosphorylation events (unlike PDGF RTK where they trans-autophosphorylate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

do all RTKs act as their own scaffold proteins

A

Yes, they all become phosphorylated on their tails, and they become that way to act as scaffolds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what are 3 proteins in PDGF receptor

A

PI 3 Kinase, GAP, phospholipase c-gamma (PLCy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what do each of these signaling proteins do

A

play a role in PDGF receptor signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what do these signaling proteins recognize

A

phosphorylated tyrosines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what happens upon phosphorylation

A

creates binding sites that proteins have evolved to recognize and glue themselves on, formation of signaling complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what do signaling proteins bind to specifically

A

not random phosphorylated tyrosines; signaling protein is recognizing a specific subset of phosphorylated tyrosines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what does PLC gamma recognize

A

2 phosphorylated tyrs at the tip: position 1009, 1021

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what does GAP recognize

A

phosphorylated tyrosine at position 771

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

describe binding sites

A

not just any phosphorylated tyrosines; specific ones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

so what specific piece of info do they look for when choosing which tyrosine to bind

A

AAs; tyrosines have neighbors and structural info along proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

can serine and threonine be phosphorylated

A

yes; act as docking sites for proteins when this happens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

in example what binds to phosphorylated tyrosine

A

SH2 domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

if a protein has SH2 domain what can it do

A

bind phosphorylated tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

but SH2 domain is not just recognizing tyrosine; what else?

A

second binding site within Sh2 domain specifically recognizing AA very close to the one getting pohspohrylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

basically what happens w/ SH2 domains

A

recognizes phosphorylated tyrosine plus the amino acid right beside it

52
Q

what do you get because of the large numbers of AAs

A

combinatorial diversity

53
Q

describe the binding sites in Sh2 domain

A

2 binding pockets held closely together within binding site of protein; one for phosphotyrosine in question, other for amino acid side chain immediately next to it

54
Q

what is the example pathway for RTKs

A

ras map kinase signaling pathway

55
Q

G proteins are helpful for GPCRs, but what else

A

RTKs

56
Q

what g proteins involved in RTKs

A

g alpha, beta, gamma

57
Q

what g protein has GTP binding ability

A

g alpha

58
Q

describe G alpha

A

large g protein

59
Q

what is ras

A

small g protein; Ras GTPase

60
Q

what is ras; in depth

A

ras monomeric GTPases (monomers, different from heterotrimeric G proteins)

61
Q

what are examples of Ras superfamily

A

Rac and Rho

62
Q

what does hyperactivation of Rho cause

A

forces cell to be contractile

63
Q

what do Rac and Rho for ce cell to do

A

forces cell to make enormous lamellipodia (actin based structures for cell migration)

64
Q

what are gtpases hella important in

A

signal transduction

65
Q

what is one of main drivers of viral cancer and tumor growth

A

Ras

66
Q

worst oncogenes

A

ras oncogenes; 30% of cancer has mutated form of ras

67
Q

describe mutation in Ras

A

mutation in enzymatic site of GTPase

68
Q

what does GTPase do

A

hydrolyzes GTP into GDP to turn it off

69
Q

what happens if GTPase is mutated

A

can’t turn it of; always ON; keeps proliferating

70
Q

what does GTPase Ras do

A

mediates signaling by most RTKs

71
Q

in pdgf receptor what is stage 1

A

trans autophosphorylation of receptors (single site)

72
Q

what is stage 2 in pdgf

A

multiple tyrosine sites phosphorylated on both receptors
(this is immediately after trans auto phosphorylation has occurred)

73
Q

what next key player immediately after stage 1 and 2

A

Next key player: Grb2 (scaffold protein)

74
Q

what does grb2 have

A

Has an SH2 domain, able to bind that now-phosphorylated tyrosine on the tail of that receptor

75
Q

describe the SH2 binding

A

Not just recognizing that phosphorylated tyrosine, it’s recognizing phosphorylated tyrosine plus the amino acid immediately adjacent to it( that’s why its binding at the tip of the tail)

76
Q

what is sh2 binding of tyrosine to tail of receptor dependent on

A

Activation dependent binding event

77
Q

what type of protein is Grb2

A

adaptor protein (no enzymatic activity, but 2 Sh3 domains)

78
Q

describe GRB2 structure

A

scaffold protein w/ single SH2 domain and 2 SH3 domains

79
Q

what does Sh2 bind to

A

phosphorylated tyrosine in adjacent residue

80
Q

what does sh3 bind to

A

SH3 domains are binding to proline rich regions on other signaling domains (blue rectangle)

81
Q

what is indicator of Sh3 domain binding

A

AA sequence of signaling protein, and you see 3 or 4 or 5 prolines adjacent to each other but nothing in between

82
Q

what is next thing that joins party

A

sos

83
Q

describe sos

A

proline rich domains, has other binding sites

84
Q

what is activity of sos

A

acts as a gef

85
Q

what happens to sos upon binding

A

becomes active, now able to act as a Gef for inactive Ras

86
Q

describe Ras protein

A

small GTPase protein, monomer (lipid anchor)

87
Q

what is purpose of lipid anchor

A

to hold it against plasma membrane, right place and right time

88
Q

what is inactive Ras protein bound to

A

GDP

89
Q

what happens after GEF activity

A

conformational change denoted by outward bulge of protein, and red lines radiating away from it

89
Q

what does inactive Ras bump into

A

interacts w/ Sos GEF domain that release GDP into cytoplasm (where it’s recycled back into GTP at some point)

90
Q

what happens after GEF & conformational change

A

activates downstream signaling partners

91
Q

what does Ras activate

A

MAP kinases

92
Q

what does MAP stand for

A

mitogen activated kinase

93
Q

where is active Ras protein

A

still anchored in plasma membrane

94
Q

what does active Ras bump into

A

MAP kinase kinase kinase (Raf)

95
Q

what does Ras bumping into raf do

A

triggers conformational change, raf is activated

96
Q

are these kinases RTKs?

A

no; MAP kinase phosphorylates serine and threonine residues

97
Q

what happens when Raf is activated

A

phosphorylates downstream targets

98
Q

Raf phosphorylates twice to get

A

Mek

99
Q

what comes after Mek

A

Erk

100
Q

where is all this happening

A

plasma membrane (raf stuck at plasma membrane where ras is anchored)

101
Q

what happens after Raf

A

all the steps after raf can go to cytoplasm

102
Q

where is Mek floating around

A

Mek is floating around cytoplasm, bumps into active Raf and becomes phosphorylated

103
Q

what happens after Mek is phosphorylated to Erk

A

Now they leave plasma membrane and go deeper in the cell

104
Q

what does Erk act on

A

acts on diff targets to change protein activity and gene expression

105
Q

what is ras map kinase pathway associated w/

A

cell proliferation

106
Q

how many phosphorylation events per activation

A

2

107
Q

how many receptors activated simultaneously in PDGF

A

multiple

108
Q

how do you avoid jumbled signals or cross talk

A

scaffold proteins; diff pathways, diff downstream partners

109
Q

both pathways in yeast share kinase A, what prevents them from getting singals wrong

A

scaffold 1 (mating) has binding site for Kinase A, then B, then C

scaffold 2 has kinase A, then itself has a kinase domain that activates kinase D

110
Q

what does scaffold itself bringing substrate next to kinase A

A

in glycerol synthesis pathway it has no opportunity to phosphorylate anything else except next step in the pathway

111
Q

what do Rho family GTPases do

A

functionally couple cell surface receptors to cytoskeleton

112
Q

what is the output of signaling pathway controlling retraction

A

actomyosin contractility

113
Q

what is actomyosin contractility

A

myosin-mediated actin filament contraction

114
Q

what does actomyosin contractility cause

A

growth cone collapse (tries to have 2nd shot at getting where it wants to go)

115
Q

what mediates growth cone collapse

A

contact depending signaling

116
Q

where is ligand

A

anchored on surface of adjacent cell; already dimerized –> trans autophosphorylation (RTKs)

117
Q

what is receptor

A

EphA4

118
Q

what is ligand

A

ephrin A1

119
Q

what does dimerized ligand do

A

dimerizes EphA4 receptor, trans-autophosphorylation of cytoplasmic tails

120
Q

what is job of signaling proteins

A

phosphorylate Rho GEF

121
Q

what is Rho

A

small GTPase, controls actomyosin contractility

122
Q

what does phosphorylating Rho do

A

activate Rho by triggering exchange of GDP with GTP

123
Q

what does activated Rho do

A

binds downstream effectors leads to massive actomyosin contractility and retraction of growth cone

124
Q

where is ephexin

A

not bound to plasma membrane, anchored close enoughwh

125
Q

where does rhoA diffuse

A

thru plasma membrane, gets contact w/ ephexin

126
Q

what would happen if ephexin was mutated

A

no longer bound to receptor but it was still active, much less likely to be able to activate RhoA b/c its not in the right place

bio 211 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions