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Cell and Molecular Biology > Module 5: Cell Signaling: 3 Signaling through Enzyme-Coupled Receptors > Flashcards

Module 5: Cell Signaling: 3 Signaling through Enzyme-Coupled Receptors Flashcards

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1
Q

What type of protein structure do enzyme-coupled receptors have?

A

Transmembrane proteins

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2
Q

Where is the ligand-binding domain of enzyme-coupled receptors located?

A

Outer surface

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3
Q

In enzyme-coupled receptors, it has intrinsic enzyme activity or associates directly with an enzyme

A

cytosolic domain

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4
Q

How many transmembrane segments do enzyme-coupled receptors typically have?

A

1

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5
Q

What is the most common class of enzyme-coupled receptors?

A

Receptor Tyrosine Kinases (RTKs)

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6
Q

How do RTKs activate signaling pathways?

A

Through phosphorylation

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7
Q
  • How many human RTKs are classified into structural subfamilies?
  • How many structural subfamilies are there for human RTKs?
A
  • 60
  • 20
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8
Q

What does each RTK subfamily correspond to?

A

A specific protein-ligand family

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9
Q

What activates the tyrosine kinase domain on the cytosolic side of the receptor?

A

Binding of the signal protein to the ligand-binding domain on the extracellular side

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10
Q

What happens when the signal protein binds to the receptor?

A

triggers activation inside the cell

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11
Q

What is the result of phosphorylation in RTK signaling?

A

Formation of phosphotyrosine docking sites

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12
Q

What occurs when ligands bind to RTKs?

A

Receptors dimerize

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13
Q
  • Brings the two cytoplasmic kinase domains together, promoting their activation.
  • allowing them to phosphorylate each other on specific tyrosines
  • close proximity leads to the phosphorylation of each other
A

RTK dimerization/dimerization

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14
Q

What promotes conformational changes in the kinase domains of RTKs?

A

Activation of the kinase domains

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15
Q
  • What is an important exception to the transautophosphorylation mechanism?
  • This receptor’s kinase activation is through interactions outside active sites rather than phosphorylation
A

Epidermal Growth Factor (EGF) receptors

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16
Q

What happens to signaling proteins when they bind to a phosphorylated site on RTKs?

A

become activated

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17
Q

In RTK signaling, it serves as a switch to trigger the assembly of an intracellular signaling complex

A

receptor phosphorylation

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18
Q

On RTK’s, it recruits and organizes proteins for downstream signal propagation

A

phosphorylated sites

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19
Q

How do many RTKs exist in the absence of extracellular signals?

A
  • monomers with inactive internal kinase domains
  • or Inactive monomer
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20
Q

On the dimerization in the kinase domains of RTKs, the close proximity leads to the __ of each other

A

phosphorylation

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21
Q

What are the two effects of phosphorylation in RTKs? (2)

A

1) Promotes complete activation of the kinase domains
2) Generates docking sites for intracellular signaling proteins

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22
Q

__ created by tyrosine phosphorylation result in the formation of large signaling complexes that broadcast signals along multiple signaling pathways

A

docking sites

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23
Q

In some RTKs that normally exist as dimers when ligand binding happens, it causes a __ __ that brings the internal kinase domains closer together

A

conformational change

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24
Q

What is a common mechanism of activation for many RTKs?

A

Transautophosphorylation

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25
Q

In EGF receptor activation, what are the two types of kinase domains in the asymmetrical dimer? (2)

A

1) Activator
2) Receiver

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26
Q

In EGF receptor activation, what do the phosphorylated tyrosines in the C-terminal tails generate for intracellular signaling proteins?

A

Docking sites

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27
Q
  • Families of monomeric GTPases
  • relay signals from cell-surface receptors
  • can coordinately spread the signal along several distinct
    downstream signaling pathways – signaling hub
A

Ras superfamily

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28
Q

What are the types of Ras proteins found in humans? (3)

A
  • H-Ras
  • K-Ras
  • N-Ras
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29
Q

Contains one or more covalently attached lipid groups (anchors them to the plasma membrane)

A

Ras proteins

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30
Q

Required when RTKs signal to the nucleus to stimulate cell proliferation or differentiation

A

Ras proteins

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31
Q

What percentage of human tumors express hyperactive mutant forms of Ras?

A

30%

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32
Q

What expresses hyperactive mutant forms of Ras in humans (30% of it)?

A

tumors

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33
Q

What do mutations in Ras proteins lead to?

A

Uncontrolled cancer cell proliferation

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34
Q

What does Ras function as?

A

molecular switch

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35
Q

There are 2 distinct conformational states that Ras cycles between. What state when GTP is bound and when GDP is bound? (2)

A
  • active
  • inactive
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36
Q

What are the two classes of signaling proteins that regulate Ras activity? (2)

A
  • Ras guanine nucleotide exchange factors (Ras-GEFs)
  • Ras GTPase-activating proteins (Ras-GAPs)
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37
Q

Activate Ras by promoting the dissociation of GDP and uptake of GTP.

A

Ras guanine nucleotide exchange factors (Ras-GEFs)

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38
Q

Inactivate Ras by hydrolyzing bound GTP.

A

GTPase-activating proteins (Ras-GAPs)

39
Q

They are resistant to Ras-GAPs and remain in the GTP-bound active state.

A

hyperactive mutant forms of Ras

40
Q

Why is Ras activity regulation important? (2)*

A
  • normal cellular processes
  • preventing cancer
41
Q

What is the result of Ras being locked in the active state? (2) *

A
  • Uncontrolled cell proliferation
  • cancer development
42
Q

How do RTKs activate Ras? (2)

A
  • activating a Ras-GEF
  • inhibiting a Ras-GAP
43
Q

What is the effect of the loss of function of a Ras-GEF similar to?

A

loss of function of Ras

44
Q

What is the GEF that mediates Ras activation by RTKs?

A

Sevenless (Sev)

45
Q

It is required for the formation of the photoreceptor cell R7. (and in what organism?*)

A

Sevenless (Sev) in Drosophila*

46
Q

What is the Ras-GEF involved in Ras activation?

A

Son-of-sevenless (Sos)

47
Q

In Ras activation, it is an adaptor protein that links the Sev receptor to the Sos protein.

A

Grb2 (Growth factor receptor-bound protein 2)

48
Q

Promote Ras activation, by binding to the activated receptor via Grb2, facilitating Ras activation.

A

Son-of-sevenless (Sos)

49
Q

Ras activates various other signaling proteins to relay the signal __.

A

downstream

50
Q

What domains does Grb2 contain that link it to Ras activation? And where do they bind? (2)*

A
  • SH2 domain (binds to the activated receptor)
  • SH3 domains (bind to Sos).
51
Q

What are the characteristics of tyrosine phosphorylation and Ras activation in terms of duration?

A

short-lived

52
Q

What reverses tyrosine phosphorylations?

A

Tyrosine-specific protein phosphatases

53
Q

What induces activated Ras to inactivate itself?

A

Ras GTPase-activating proteins (Ras GAPs)

54
Q

What is required to stimulate cells to proliferate or differentiate?

A

longer-lasting signal

55
Q

What is the name of the system that conveys longer-lasting signals downstream?
- required to stimulate cells to proliferate or differentiate

A

Mitogen-activated protein kinase module (MAP kinase module)

56
Q

What are the three components of the MAP kinase module? (3)

A
  • MAPK (Erk)
  • MAPKK (Mek)
  • MAPKKK (Raf)
57
Q

How does MAP kinase relay signals downstream?

A

By phosphorylation.

58
Q

Enters the nucleus and phosphorylates the transcription regulatory complex → immediate early genes (transcription regulators)

A

MAPK (Erk)

59
Q

Transcription regulators phosphorylated by Erk.

A

immediate early genes

60
Q

In the MAP kinase module, what phosphorylates and activates MAPK?

A

MAPKK (Mek)

61
Q

in the MAP kinase module, what phosphorylates and activates MAPKK?

A

MAPKKK (Raf)

62
Q

They are protein kinases that mainly phosphorylate serines and threonines.*

A

components of the MAP kinase module

63
Q

It directly activates MAPKKK, initiating the phosphorylation cascade.*

A

Ras

64
Q

They convey signals from the cell surface to the nucleus and alters the pattern of gene expression

A

Ras-MAP-kinase signaling pathways

65
Q

What technique was used to study transient activation of Ras?*

A

FRET (Fluorescence Resonance Energy Transfer)

66
Q

What does Erk (MAPK) phosphorylate in the nucleus?*

A

Transcription regulators

67
Q

What does Erk (MAPK) phosphorylate in the cytoplasm?*

A

Other protein kinases

68
Q

Where does Ras recruit Raf to help activate it?*

A

plasma membrane

69
Q

What are the outcomes of MAP kinase module activation? (2)*

A
  • Changes in protein activities
  • changes in gene expression
70
Q

mediates different responses in the same cell

A

MAP kinase modules

71
Q

What prevents cross-talk between parallel MAP kinase modules?

A

Scaffold proteins

72
Q

How many parallel MAP kinase modules can operate in a mammalian cell?

A

5 parallel MAP kinase modules

73
Q

What are the total numbers of MAP kinases, MAPKKs, and MAPKKKs in mammalian cells? (3)

A
  • 2 MAP kinases
  • 7 MAPKKs
  • 7 MAPKKKs
74
Q

Which MAP kinases are activated by cell stresses such as UV irradiation, heat shock, and osmotic stress? (2)

A

JNK and p38

C-jun-N-terminal kinase (JNK)

75
Q

They ensure response specificity by forming complexes with MAP kinase components.*

A

Scaffold proteins

76
Q

It reduces opportunities for amplification and spreading of the signal to different parts of the cell.

A

Scaffold proteins

77
Q

What is the main advantage of the scaffold protein strategy in MAP kinase modules?*

A

Precision and avoidance of cross-talk between pathways

78
Q

Why is there no cross-talk between the mating and osmolarity pathways in MAP kinase modules present in budding yeast?*

A

Different scaffold proteins bind each module and receptor.

79
Q
  • regulate both the actin and microtubules cytoskeleton controlling
    cell shape, polarity, motility, and adhesion;
  • they also regulate cell cycle progression, gene transcription, and membrane transport;
  • guidance of cell migration and nerve axon outgrowth
A

Rho family monomeric GTPases

80
Q

What cytoskeletal structures do Rho family GTPases regulate? (2)

A
  • actin
  • microtubules
81
Q

What cellular processes do Rho family GTPases control? (7)

A
  • Cell shape
  • cell polarity
  • cell motility
  • cell adhesion
  • cell-cycle progression
  • gene transcription
  • membrane transport
82
Q

What cellular processes do Rho family GTPases guide? (2)

A
  • cell migration
  • nerve axon outgrowth
83
Q

Name the three best-characterized members of the Rho family. (3)

A
  • Rho
  • Rac
  • Cdc42
84
Q

What proteins activate Rho family GTPases?

A

Guanine nucleotide exchange factors (GEFs).

85
Q

What proteins inactivate Rho family GTPases?

A

GTPase-activating proteins (GAPs).

86
Q

What state are Rho family GTPases in the cytosol if bound to guanine nucleotide dissociation inhibitors (GDIs)?

A

inactive

87
Q

They prevent the GTPases from interacting with their Rho GEFs at the plasma membrane.*

A

guanine nucleotide dissociation inhibitors (GDIs)

88
Q

What extracellular signaling protein family activates the Eph family of RTKs?

A

Ephrin family

89
Q

Guides the migrating tip of the axon (growth cone) to its muscle target in motor neurons

A

Eph family of RTKs

90
Q

What happens when an ephrin protein binds to an Eph receptor?

A

Eph receptor is activated.

91
Q

What is the effect of Eph receptor activation on growth cones?

A

Growth cone collapse, repelling them from inappropriate regions and keeping them on track.

92
Q

activate RhoA (Rhoa-GTP)

A

Rho-GEF ephexin

93
Q

What Rho GEF is involved in ephrin-Eph signaling?

A

ephexin

94
Q

What protein does ephexin activate in ephrin-Eph signaling?

A

RhoA (RhoA-GTP)

Cell and Molecular Biology (20 decks)

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