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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

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
In EGF receptor activation, what are the two types of kinase domains in the asymmetrical dimer? (2)
1) Activator 2) Receiver
26
In EGF receptor activation, what do the phosphorylated tyrosines in the C-terminal tails generate for intracellular signaling proteins?
Docking sites
27
- Families of monomeric GTPases - relay signals from cell-surface receptors - can coordinately spread the signal along several distinct downstream signaling pathways – *signaling hub*
Ras superfamily
28
What are the types of Ras proteins found in humans? (3)
- H-Ras - K-Ras - N-Ras
29
Contains one or more covalently attached lipid groups (anchors them to the plasma membrane)
Ras proteins
30
Required when RTKs signal to the nucleus to stimulate cell proliferation or differentiation
Ras proteins
31
What percentage of human tumors express hyperactive mutant forms of Ras?
30%
32
What expresses hyperactive mutant forms of Ras in humans (30% of it)?
tumors
33
What do mutations in Ras proteins lead to?
Uncontrolled cancer cell proliferation
34
What does Ras function as?
molecular switch
35
There are 2 distinct conformational states that Ras cycles between. What state when GTP is bound and when GDP is bound? (2)
- active - inactive
36
What are the two classes of signaling proteins that regulate Ras activity? (2)
- Ras guanine nucleotide exchange factors (Ras-GEFs) - Ras GTPase-activating proteins (Ras-GAPs)
37
Activate Ras by promoting the dissociation of GDP and uptake of GTP.
Ras guanine nucleotide exchange factors (Ras-GEFs)
38
Inactivate Ras by hydrolyzing bound GTP.
GTPase-activating proteins (Ras-GAPs)
39
They are resistant to Ras-GAPs and remain in the GTP-bound active state.
hyperactive mutant forms of Ras
40
Why is Ras activity regulation important? (2)*
- normal cellular processes - preventing cancer
41
What is the result of Ras being locked in the active state? (2) *
- Uncontrolled cell proliferation - cancer development
42
How do RTKs activate Ras? (2)
- activating a Ras-GEF - inhibiting a Ras-GAP
43
What is the effect of the loss of function of a Ras-GEF similar to?
loss of function of Ras
44
What is the GEF that mediates Ras activation by RTKs?
Sevenless (Sev)
45
It is required for the formation of the photoreceptor cell R7. (and in what organism?*)
Sevenless (Sev) in Drosophila*
46
What is the Ras-GEF involved in Ras activation?
Son-of-sevenless (Sos)
47
In Ras activation, it is an adaptor protein that links the Sev receptor to the Sos protein.
Grb2 (Growth factor receptor-bound protein 2)
48
Promote Ras activation, by binding to the activated receptor via Grb2, facilitating Ras activation.
Son-of-sevenless (Sos)
49
Ras activates various other signaling proteins to relay the signal __.
downstream
50
What domains does Grb2 contain that link it to Ras activation? And where do they bind? (2)*
- SH2 domain (binds to the activated receptor) - SH3 domains (bind to Sos).
51
What are the characteristics of tyrosine phosphorylation and Ras activation in terms of duration?
short-lived
52
What reverses tyrosine phosphorylations?
Tyrosine-specific protein phosphatases
53
What induces activated Ras to inactivate itself?
Ras GTPase-activating proteins (Ras GAPs)
54
What is required to stimulate cells to proliferate or differentiate?
longer-lasting signal
55
What is the name of the system that conveys longer-lasting signals downstream? - required to stimulate cells to proliferate or differentiate
Mitogen-activated protein kinase module (MAP kinase module)
56
What are the three components of the MAP kinase module? (3)
- MAPK (Erk) - MAPKK (Mek) - MAPKKK (Raf)
57
How does MAP kinase relay signals downstream?
By phosphorylation.
58
Enters the nucleus and phosphorylates the transcription regulatory complex → immediate early genes (transcription regulators)
MAPK (Erk)
59
Transcription regulators phosphorylated by Erk.
immediate early genes
60
In the MAP kinase module, what phosphorylates and activates MAPK?
MAPKK (Mek)
61
in the MAP kinase module, what phosphorylates and activates MAPKK?
MAPKKK (Raf)
62
They are protein kinases that mainly phosphorylate serines and threonines.*
components of the MAP kinase module
63
It directly activates MAPKKK, initiating the phosphorylation cascade.*
Ras
64
They convey signals from the cell surface to the nucleus and alters the pattern of gene expression
Ras-MAP-kinase signaling pathways
65
What technique was used to study transient activation of Ras?*
FRET (Fluorescence Resonance Energy Transfer)
66
What does Erk (MAPK) phosphorylate in the nucleus?*
Transcription regulators
67
What does Erk (MAPK) phosphorylate in the cytoplasm?*
Other protein kinases
68
Where does Ras recruit Raf to help activate it?*
plasma membrane
69
What are the outcomes of MAP kinase module activation? (2)*
- Changes in protein activities - changes in gene expression
70
mediates different responses in the same cell
MAP kinase modules
71
What prevents cross-talk between parallel MAP kinase modules?
Scaffold proteins
72
How many parallel MAP kinase modules can operate in a mammalian cell?
5 parallel MAP kinase modules
73
What are the total numbers of MAP kinases, MAPKKs, and MAPKKKs in mammalian cells? (3)
- 2 MAP kinases - 7 MAPKKs - 7 MAPKKKs
74
Which MAP kinases are activated by cell stresses such as UV irradiation, heat shock, and osmotic stress? (2)
**JNK** and **p38** | C-jun-N-terminal kinase (JNK)
75
They ensure response specificity by forming complexes with MAP kinase components.*
Scaffold proteins
76
It reduces opportunities for amplification and spreading of the signal to different parts of the cell.
Scaffold proteins
77
What is the main advantage of the scaffold protein strategy in MAP kinase modules?*
Precision and avoidance of cross-talk between pathways
78
Why is there no cross-talk between the mating and osmolarity pathways in MAP kinase modules present in budding yeast?*
Different scaffold proteins bind each module and receptor.
79
- 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
Rho family monomeric GTPases
80
What cytoskeletal structures do Rho family GTPases regulate? (2)
- actin - microtubules
81
What cellular processes do Rho family GTPases control? (7)
- Cell shape - cell polarity - cell motility - cell adhesion - cell-cycle progression - gene transcription - membrane transport
82
What cellular processes do Rho family GTPases guide? (2)
- cell migration - nerve axon outgrowth
83
Name the three best-characterized members of the Rho family. (3)
- Rho - Rac - Cdc42
84
What proteins activate Rho family GTPases?
Guanine nucleotide exchange factors (GEFs).
85
What proteins inactivate Rho family GTPases?
GTPase-activating proteins (GAPs).
86
What state are Rho family GTPases in the cytosol if bound to guanine nucleotide dissociation inhibitors (GDIs)?
inactive
87
They prevent the GTPases from interacting with their Rho GEFs at the plasma membrane.*
guanine nucleotide dissociation inhibitors (GDIs)
88
What extracellular signaling protein family activates the Eph family of RTKs?
Ephrin family
89
Guides the migrating tip of the axon (growth cone) to its muscle target in motor neurons
Eph family of RTKs
90
What happens when an ephrin protein binds to an Eph receptor?
Eph receptor is activated.
91
What is the effect of Eph receptor activation on growth cones?
**Growth cone collapse**, repelling them from inappropriate regions and keeping them on track.
92
activate RhoA (Rhoa-GTP)
Rho-GEF ephexin
93
What Rho GEF is involved in ephrin-Eph signaling?
ephexin
94
What protein does ephexin activate in ephrin-Eph signaling?
RhoA (RhoA-GTP)

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