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MFoM > 08c: Cell Signaling > Flashcards

08c: Cell Signaling Flashcards

1
Q

Receptor tyrosine kinases have which structure? And which domains?

A

Single-pass transmembrane receptors; ligand-binding domain outside cell and kinase domain inside cell

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2
Q

Receptor tyrosine kinases bind (X). What is their primary function?

A

X = growth factors

Control rate of cell growth and proliferation

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3
Q

T/F: all RTK ligand so control cell proliferation.

A

False - insulin receptor does not

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4
Q

First step in in RTK signaling (once ligand(s) bind):

A

Dimerization of the receptors

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5
Q

RTK ligands are (monomers/dimers/other).

A

Can be either monomers or dimers

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6
Q

After ligand binds and RTK receptors (dimerize/separate), which event takes place?

A

Dimerize;

Phosphorylation of one receptor by another (and sometimes vice versa)

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7
Q

RTK are phosphorylated on which residue(s) and domain(s)?

A

Tyrosine residues on their kinase (intracellular) domains

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8
Q

List the key protein (X) that recognize phosphorylated RTK.

A

X = domains

  1. SH2
  2. PTB
  3. SH3
  4. PH
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9
Q

SH2 domains specifically recognize:

A

Phosphorylated tyrosine, followed by X, X, Hy

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10
Q

PTB domains specifically recognize:

A

N, X, P, Y(phosphorylated)

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11
Q

SH3 domains specifically recognize:

A

Proline-rich sequences

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12
Q

PH domains specifically recognize:

A

Phosphorylated lipids

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13
Q

T/F: One RTK can interact with several domains, activating several pathways, at once.

A

True

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14
Q

Overall result of stimulation of MAP kinase pathway.

A

Increased cell proliferation

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15
Q

In MAPK pathway, (X) binds activated (Y) receptors via which domain(s)?

A 
X = GRB2
Y = RTK

Via its SH2 domain

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16
Q

Bound and activated GRB2 uses its (X) domain(s) to:

A

X = two SH3 domains

To recruit and bind SOS to plasma membrane

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17
Q

GRB2 is referred to as a(n) (X) protein.

A

X = adaptor

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18
Q

SOS has which specific function?

A

GEF (GTP/GDP Exchange factor) for Ras

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19
Q

Which form of Ras is active?

A

GTP-bound Ras

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20
Q

What is the only real function of Ras? Are there enzymes that assist in its function?

A

GTPase (a small, slow one)

Yes - GAP

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21
Q

(X) recruits Ras to the cell membrane.

A

Ras is already tethered to cell membrane. No protein recruits it.

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22
Q

(X) is tethered to the cell membrane via 1 or 2 anchors, composed of (Y).

A 
X = Ras
Y = farnesyl and (sometimes) a second FA anchor
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23
Q

Activates Ras has which subsequent, immediate effect?

A

Binds Raf and recruits it to cell membrane

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24
Q

T/F: Ras and Raf must be bound to cell membrane to be active.

A

True

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25
Q

List steps in pathway that results from activated Ras.

A
  1. Ras activates and recruits Raf to PM
  2. Raf phosphorylates and activates MEK
  3. MEK phosphorylates and activates ERK
  4. ERK dimerizes and is translocated to nucleus (phosphorylates and activates transcription factors)
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26
Q

MAPK pathway can be terminated in which way(s)?

A
  1. Hydrolysis of GTP by Ras or Ras-GAP
  2. Protein phosphatase activity
  3. Internalization of receptors
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27
Q

Overall result of stimulation of PI3K pathway.

A

Increase cell growth

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28
Q

PI3Ks are a family of (X) that have which function(s)?

A

X = lipid kinases

Phosphorylated phisphatidyl inositol at C3 position

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29
Q

PI3K type (X) is important in the PI3K pathway. Describe the structure.

A

X = 1A

Has a p85 (regulatory) subunit and a p110 (catalytic) subunit

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30
Q

Describe the key steps in the PI3K pathway, involving PI3K 1A activation.

A

PI3K 1A binds two domains (via its p85 subunit SH2 domains) in the active RTK and phosphorylates PI4,5P2 at the C3 position (leading to active PIP3)

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31
Q

Activated PIP3 will bind to (X) and cause:

A

X = PDK-1 and Akt PH (regulatory, p85) domains

Conformational change that exposes Akt catalytic (p110) domain

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32
Q

Which events must occur to activate Akt?

A
  1. Bind PH domain to PIP3 (expose kinase domain)

2. Two phosphorylation events via PDK-1

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33
Q

Name two key things that are modified via (X) by activated Akt.

A

X = phosphorylation

  1. Phosphorylation of BAD
  2. Phosphorylation (and eternal inactivation) of TSC2 (a GAP for Rheb)
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34
Q

What’s TSC2? Its activity has which effect on the body?

A

GAP for Rheb; control/inhibition of cell growth

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35
Q

Inactive TSC2 means (X) is active and causing which effect(s)?

A

Rheb/GTP; activates mTORC1, which up regulates translation

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36
Q

T/F: High Rheb/GTP activity upregulates transcription.

A

False - via mTORC1 activation, it upregulates TRANSLATION

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37
Q

What kind of protein is mTORC1?

A

Ser/Thr protein kinase

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38
Q

Describe structure/domains of PLC(gamma).

A

Two SH2 domains and one PH domain

39
Q

What’s the action of an activated PLC(gamma)?

A

Cleaves PIP2 into DAG and IP3

40
Q

IP3 binds to (X) and has effect on which ion concentration(s)?

A

X = ER membrane receptors

Increases Calcium concentrations in cytosol

41
Q

DAG immediately activates:

A

PKC

42
Q

Largest family of receptors:

A

G Protein Coupled Receptors

43
Q

Describe general structure of GPCRs

A

7-pass transmembrane receptors (N terminus outside cell, C terminus inside)

44
Q

A water-soluble ligand will bind to (X) on GPCRs. A hydrophobic ligand will bind to (Y) on GPCRs.

A 
X = extra cellular domains
Y = transmembrane domains
45
Q

GPCR typically associated with (X)-protein. Which subunits make up this protein?

A

X = G

Usually 3 (alpha, beta and gamma) subunits

46
Q

Alpha subunit on G-protein is a(n) (X) that binds the other subunits when it is in which state?

A

X = GTPase

Binds beta and gamma when in GDP form, not GTP form

47
Q

Which subunit(s), if any, in G protein are anchored to cell membrane?

A

Alpha has anchor at N terminus;

Beta-gamma complex has anchor at C terminus of gamma

48
Q

Binding of ligand to GPCR will allow it to act on G protein (X) subunit in which specific way?

A

X = alpha

Acts as GEF, then allowing GTP-bound alpha subunit to dissociate from beta-gamma complex

49
Q

The best-studied isoforms of alpha subunit are (X). What effects do they have?

A

X = a(s) and a(I)

Affect adenylyl cyclase activity via stimulation (alpha-s) or inhibition (alpha-I)

50
Q

What is the function of adenylyl cyclase?

A

Converts ATP to 3’-5’ cAMP

51
Q

PDE can be activated by (X) and functions to (increase/reduce) concentration of which key signaling molecule? Via which mechanisms?

A

X = certain G protein alpha subunits

Reduces 3’,5’-cAMP concentration in cell by cleaving it into 5’-AMP (no signaling importance)

52
Q

Notable target of activated beta-gamma G protein complex

A

PI3K type 1B (same action as 1A, but activated differently)

53
Q

Normal cAMP concentration in cell:

A

0.1 microM

54
Q

(X) binds PKA on which subunits? What occurs?

A

X = cAMP

On its two regulatory subunits, causing conformational change and exposure of its two catalytic subunits

55
Q

PKA is which type of protein?

A

Ser/Thr protein kinase

56
Q

Give example of cooperative binding in a kinase.

A

cAMP binding PKA regulatory subunits

57
Q

(X) catalytic subunits, once exposed, at as two separate monomers.

A

X = PKA

58
Q

Glucose metabolism can be controlled by cAMP in which way?

A
  1. cAMP controls activation of PKA

2. PKA regulates glucose metabolism via phosphorylation of phosphorylase kinase and glycogen synthase

59
Q

Phosphorylase kinase is involved in (X) and is controlled by (Y).

A 
X = glucose metabolism
Y = PKA
60
Q

PKA controls which processes?

A
  1. Glucose metabolism
  2. Lipolysis
  3. Transcription
61
Q

Lipid metabolism can be controlled by cAMP in which way?

A
  1. cAMP controls activation of PKA

2. PKA regulates lipolysis via phosphorylation of hormone-sensitive lipase and perilipin

62
Q

CREB, located in (X), can be activated by (high/low) cAMP through which mechanism?

A

X = nucleus
High

Activates PKA; monomeric catalytic subunit can enter nucleus and phosphorylate/activate CREB

63
Q

Up-regulation of CREB will affect which process?

A

Up-regulate transcription

64
Q

PLC(beta), like (X), has which action?

A

X = PLC(gamma)

Cleaves PIP2 into IP3 and DAG

65
Q

Binding of (X) to receptors on the (Y) organelle increases calcium concentration to:

A 
X = IP3
Y = ER

from 0.1 microM to 1 microM and higher

66
Q

How does calcium concentration return to baseline?

A

Calcium-ATPases pump calcium either out of cell or back into ER

67
Q

Calcium binds to a specific sensor called (X), which is present in (free/bound) form.

A

X = calmodulin

Can be in either form

68
Q

Upon binding (X) number of calcium atoms, (Y) changes conformation and activates (Z).

A 
X = 4
Y = calmodulin
Z = calcium/calmodulin-dependent kinase
69
Q

Upon binding calmodulin, the enzyme (X) will:

A

X = ca/calmodulin-dependent kinase

phosphorylate and activate itself

70
Q

How does (high/low) calcium level affect deactivation of ca/calmodulin-dependent kinase?

A

Ca level won’t affect activated kinase - only phosphatases can deactivate it

71
Q

Describe feedback inhibition of (X) by PKA or PKC.

A

X = GPCRs

phosphorylate third intracellular loop (where receptor binds alpha subunit)

72
Q

What are GRKs? What is their immediate action?

A

GPCR kinases that phosphorylate the receptors at third intracellular loop or at C terminus

73
Q

GPCR phosphorylation at C terminus results in which event(s)?

A

Interaction with arrestins, which:

  1. interfere with G protein binding
  2. recruit clathrin to promote internalization of GPCRs
74
Q

Clathrin is promoted by (X) and functions in (Y).

A 
X = arrestins
Y = internalization of GPCR
75
Q

If ligand is bound to GPCR, can the action still be inhibited?

A

Yes - GRKs only phosphorylate ligand-bound GPCRs

76
Q

Black and white vision involves the (RTK/GPCR) called:

A

GPCR; rhodopsin

77
Q

In rods, (X) is bound to (Y) which, upon exposure to light, converts to (Z).

A 
X = rhodopsin
Y = 11-cis retinal
Z = all-trans retinal
78
Q

Conformational change to all-trans retinal has which effect in rods?

A

GEF activity of rhodopsin on Transducin (the G protein)

79
Q

What’s the name of the G protein involved in black and white vision?

A

Transducin

80
Q

Liberated (X) subunit of transducin affects which protein(s)?

A

X = alpha

Activates cGMP PDE, lowering cGMP levels

81
Q

In color vision, different colors have different (X) bound to (Y) and affected by its conformational change.

A 
X = opsins
Y = retinal
82
Q

We have opsins for which colors?

A

Blue, green, red

83
Q

Whats the name of the (RTK/GPCR) in smell?

A

There are hundreds to thousands!

84
Q

G protein called Golf is involved in:

A

olfactory sense

85
Q

Subunit alpha-golf activates:

A

adenylyl cyclase

86
Q

T/F: cAMP can only have an effect by binding to PKA.

A

False - example is in olfactory senses

87
Q

Alpha-golf affects concentration of (X), which (opens/closes) (Y).

A

X = cAMP
Opens
cAMP-gated sodium channels (depolarization)

88
Q

What are the basic tastes?

A

Sweet, sour, salty, umami, bitter

89
Q

Which tastes don’t require receptors? How are they mediated?

A

Sour and salty; mediated by hydrogen and sodium ion channels

90
Q

Which tastes share family of (X) receptors? What are the names of the receptors?

A

X = GPCR
Sweet and umami

T1R1, T1R2, T1R3

91
Q

T1R2/T1R3 heterodimer responsible for:

A

sweet taste

92
Q

T1R1/T1R3 heterodimer responsible for:

A

umami taste

93
Q

G protein involved in taste is (X) and activates (Y).

A 
X = gustducin
Y = PLC(beta)

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