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BIO230 Final > Week 11 > Flashcards

Week 11 Flashcards

1
Q

What are the two primary mechanisms of signaling via enzyme-coupled receptors?

A
  1. Phosphorylation
  2. Proteolysis
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2
Q

What occurs during the phosphorylation mechanism of signaling?

A

Signal perception triggers the activation of receptor kinases or receptor-associated kinases

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3
Q

Name the three types of receptors involved in the phosphorylation mechanism.

A

a) Receptor tyrosine kinases (RTKs)
b) Tyrosine kinase-associated receptors
c) Receptor serine/threonine kinases

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4
Q

Describe the proteolysis mechanism in enzyme-coupled receptor signaling.

A

Signal perception triggers the cleavage or degradation of proteins

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5
Q

Why are receptor tyrosine kinases important?

A
  • essential in mammals
  • they mediate diverse funtions by responding to various extracellular signals through ligand binding
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6
Q

What are the main structural components of RTKs?

A
  1. Different extracellular domain (binds different ligands)
  2. Transmembrane domain
  3. Intracellular tyrosine kinase domain
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7
Q

What role does the intracellular tyrosine kinase domain play in RTKs?

A

phosphorylates specific target proteins at tyrosine residues

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8
Q

What is transautophosphorylation in the context of RTKs?

A
  • a process where activated RTKs phosphorylate themselves on tyrosine residues
  • enhancing their activity and creating docking sites for downstream signaling proteins
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9
Q

How do RTKs interact with other signaling molecules?

A

Activated RTKs can recruit various signaling molecules through specific binding domains
- act as a scaffold protein

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10
Q

What are the two types of domains that signaling proteins can use to bind to receptor tyrosine kinases (RTKs)?

A

SH2 or PTB

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11
Q

How many binding sites does each SH2 domain have, and what do they recognize?

A
  1. One site recognizes the phosphorylated tyrosine.
  2. The second site recognizes nearby amino acids.
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12
Q

Why is the specificity of SH2 domains important in cellular signaling?

A

ensures that they bind only to specific phosphorylated proteins

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13
Q

What is the function of Ras-GEFs in RTK signaling?

A
  • RTK activation often activates Ras-GEFs
  • promote the exchange of GDP for GTP on Ras proteins
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14
Q

How are Ras family proteins related to GTPases?

A

Ras family proteins are a subset of monomeric GTPases, which are involved in transmitting signals from RTKs to downstream effectors

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15
Q

What is the significance of Ras in RTK signaling pathways?

A

Many RTKs signal to activate Ras monomeric GTPases

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16
Q

What is the primary role of MAP kinases in cell signaling?

A

convert a short-term receptor tyrosine kinase (RTK) activation at the cell surface into a stable, long-term change in gene expression

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17
Q

How do MAP kinases contribute to feedback mechanisms in signaling pathways?

A

provide negative feedback

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18
Q

How many MAPKKKs, MAPKKs, and MAPKs are estimated to be present in humans?

A
  • 7 MAPKKKs
  • 7 MAPKKs
    -12 MAPKs.
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19
Q

What role do scaffold proteins play in MAP kinase cascades?

A

provide specificity to MAP kinase cascades by organizing the components and ensuring that the correct signaling pathways are activated

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20
Q

What are the structural units of Drosophila compound eyes called?

A

Ommatidia

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21
Q

How many photoreceptor cells does each ommatidium contain?

A

8 photoreceptor cells (R1-R8)

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22
Q

Which photoreceptor cell is required to detect UV light in Drosophila?

A

R7

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23
Q

What type of receptor is the Sevenless (Sev) in Drosophila?

A

Receptor Tyrosine Kinase (RTK).

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24
Q

What is the ligand for the Sevenless receptor?

A

Bride of Sevenless (Boss) - R8

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25
Q

What adaptor protein is involved in the Sevenless signaling pathway?

A

Grb2 (Drk).

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26
Q

What is the role of Son of Sevenless (Sos) in the Sevenless signaling pathway?

A

acts as a Ras-GEF, facilitating the exchange of GDP for GTP on Ras proteins

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27
Q

What signaling cascade is activated by the Sevenless receptor?

A

MAP kinase cascade

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28
Q

What is the outcome of Sevenless signaling in the context of Drosophila eye development?

A

leads to the differentiation of photoreceptor cells, specifically the R7 cell

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29
Q

How does the Sevenless signaling pathway exemplify RTK signaling?

A

ligand binding, receptor activation, and downstream signaling through Ras and MAP kinases to effect cellular differentiation

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30
Q

What initiates the signaling pathway involving RTKs and phosphoinositides (PIPs)?

A

a survival factor
- RTK then activates PI3-kinase

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31
Q

What is the role of PI 3-kinase in the RTK signaling pathway?

A

converts PI(4,5)P2 to PI(3,4,5)P3

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32
Q

Which proteins bind to PI(3,4,5)P3 in the RTK signaling pathway?

A

PDK1 and Akt

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33
Q

What is the role of PDK and mTORC2 in the signaling pathway?

A

phosphorylate Akt

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34
Q

What does Akt phosphorylate, and what is the outcome of this phosphorylation?

A

phosphorylates Bad, which leads to the release of Bcl2 to inhibit apoptosis

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35
Q

Is there a crosstalk between RTK and GPCR signaling?

A

Yes
- indicating they are not completely separate.

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36
Q

What are tyrosine-kinase-associated receptors?

A

receptors that do not have intrinsic kinase activity but associate with cytoplasmic tyrosine kinases to transmit signals (Cytokine receptors.)

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37
Q

How do tyrosine-kinase-associated receptors transmit signals?

A

associate with cytoplasmic tyrosine kinases
- which then facilitate signaling through mechanisms such as transautophosphorylation

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38
Q

What are receptor serine/threonine kinases (RSTKs)?

A

a type of enzyme-coupled receptor that transmits signals by phosphorylating serine and/or threonine residues in target proteins

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39
Q

How do receptor serine/threonine kinases compare to receptor tyrosine kinases (RTKs)?

A

Similar:
- extracellular ligand binding domain
- a transmembrane domain
- an intracellular kinase domain
- multiple receptors associate in response to signals

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40
Q

What types of residues do receptor serine/threonine kinases phosphorylate?

A

phosphorylate serine and/or threonine residues

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41
Q

What type of signaling does the Delta-Notch pathway exemplify?

A

Contact-dependent signaling

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42
Q

What are the two main mechanisms involved in Notch signaling?

A
  • Signaling via endocytosis
  • Signaling via proteolysis.
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43
Q

Where is the Notch protein synthesized?

A

ER

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44
Q

What happens to the Notch protein after it is synthesized?

A

cleaved into two pieces in the Golgi apparatus

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45
Q

What occurs to the two cleaved pieces of Notch after they are formed?

A

two pieces stay together and move to the plasma membrane

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46
Q

What is the role of the extracellular part of Notch in the signaling process?

A

directly interacts with Delta on the surface of the neighboring cell

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47
Q

What happens to the Delta-Notch complex after the interaction?

A

endocytosed into the cell expressing Delta

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48
Q

What occurs to Notch after it is endocytosed?

A

The remainder of Notch is cleaved at two additional sites after endocytosis

49
Q

What is the outcome of Notch proteolysis?

A

Notch proteolysis activates Notch target gene expression.

50
Q

Where does the cytosolic “tail” of Notch go after proteolysis?

A

moves to the nucleus

51
Q

What is the function of the Notch tail in the nucleus?

A

promotes the transcription of Notch target genes

52
Q

What effect does the activation of Notch target genes have on Delta?

A

Delta is repressed in the cell

53
Q

What is the consequence for the cell that has active Notch target genes?

A

The cell with active Notch target genes does not differentiate

54
Q

What are the key mechanisms involved in Hedgehog signaling?

A

No Hedgehog signal:
- GPCRs (G-protein coupled receptors)
- cAMP (cyclic adenosine monophosphate)
- PKA (protein kinase A)
- Proteolysis
Hedgehog signal:
- Cytoskeleton-mediated transport
- Paracrine signaling

55
Q

What is the role of Patched in Hedgehog signaling when the hedgehog signal is absent?

A

Patched is active in the cilium and inhibits Smoothened, keeps it out of the primary cilium

56
Q

Describe the role of SuFu in the absence of hedgehog signaling.

A

SuFu binds and inhibits Gli2 and Gli3

57
Q

What occurs to Gpr161 and PKA when there is no hedgehog signal?

A
  • GPCR (Gpr161) is active and promotes cAMP synthesis
  • cAMP activates PKA, which phosphorylates Gli3 causing proteolytic processing
58
Q

What happens to the remaining fragment of Gil3 when there is no hedgehog signal?

A
  • moves to the nucleus to repress expression off hedgehog target gene
59
Q

What happens to Smoothened in the presence of hedgehog signaling?

A
  • hedgehog signal binds to Patched and inactivates it
  • smoothened becomes active and moves to the tip of the primary cilium
60
Q

What happens to Gil3 when a hedgehog signal is present?

A
  • Gpr161 and PKA are inactive
  • Gil3 is not proteolytically processed so it doesn’t inhibit hedgehog target genes
61
Q

What is the fate of Gli2 when hedgehog signaling is present?

A
  • SuFu and Gil 2 move along microtubules to the tip of the primary cilium
  • Gli2 is released from SuFu due to the activation of Smoothened
  • Gli2 moves along microtubules to the nucleus and activates the hedgehog target gene
62
Q

What kind of processes are Notch and Hedgehog involved in?

A
  • multiple processes
  • Notch: bunch of differentiation processes
  • Hedgehog: bunch of developmental processes
63
Q

How are cell numbers controlled?

A
  • the cell cycle
  • programmed cell death
  • cancer
64
Q

What is the first step in the eukaryotic cell cycle?

A

Parent cellular contents are duplicated

65
Q

What occurs after the duplication of cellular contents in the eukaryotic cell cycle?

A

Cellular contents are divided into two child cells.

66
Q

Why is it important for cells to carefully control the cell cycle?

A

To protect the whole organism from errors

67
Q

What happens during the M phase?

A
  • mitosis (nuclear division)
  • cytokinesis (cytoplasmic division)
68
Q

What happens during the G1 phase?

A

a period of cell growth and preparation for DNA synthesis

69
Q

What happens during the S phase?

A

DNA replication

70
Q

What happens during the G2 phase?

A

a second growth phase that prepares the cell for mitosis

71
Q

What is the primary function of cell cycle checkpoints?

A

ensure that conditions are suitable for cell division, allowing the cell to monitor and regulate the progression

72
Q

How are cell cycle checkpoints mediated at the molecular level?

A

the controlled activity of cyclin-dependent kinases (Cdks)

73
Q

What role do cyclin-dependent kinases (Cdks) play in the cell cycle?

A

phosphorylate target proteins to promote progression through the cell cycle

74
Q

What is required for Cdks to become active?

A

require cyclins to be active

75
Q

What happens when phosphorylation occurs at cell cycle checkpoints?

A

signals the cell to proceed with the cell cycle (“go”)

76
Q

Are Cdks present throughout all stages of the cell cycle?

A

they can be but don’t always have to be

77
Q

How are cyclins regulated during the cell cycle?

A

synthesized and degraded at different stages of the cell cycle

78
Q

What determines which target proteins are phosphorylated by Cdks?

A

The combination of specific cyclins and Cdks controls which target proteins are phosphorylated

79
Q

Can the same Cdk work with different cyclins?

A

Yes, one Cdk may work with multiple cyclins, but each cyclin is specific to one stage of the cell cycle

80
Q

What are some processes targeted by active Cyclin-Cdks during the cell cycle?

A

nuclear envelope breakdown (lamin), spindle assembly (microtubule-associated proteins), and DNA replication (DNA helicases).

81
Q

Do cyclins work at multiple stages of the cell cycle?

A

No, cyclins only work at one specific stage of the cell cycle

82
Q

How are Cyclins regulated in terms of their stability?

A

can be ubiquitinated, which marks them for degradation by the proteasome

83
Q

What happens to Cdks when Cyclins are degraded?

A

When Cyclins are broken down, Cdks can no longer be activated

84
Q

Which proteins promote the degradation of M-cyclin?

A
  • APC/C
  • Cdc20
85
Q

What is the function of APC/C and Cdc20 in the cell cycle?

A
  • act as E3 ubiquitin ligases, facilitating the ubiquitination of M-cyclin
  • leading to degradation
86
Q

What determines which Cyclin-Cdk complex is active at any time?

A

synthesis and degradation of Cyclins

87
Q

What is required for Cdk activity?

A

Cyclins as they expose the T-loop

88
Q

What is the role of Cdk-Activating Kinase (CAK) in Cdk activation?

A

phosphorylates Cdk once the T-loop is exposed

89
Q

What are protein phosphatases (PP2As) and what is their function?

A

enzymes that remove phosphorylation from proteins, reversing the effects of Cyclin-Cdks

90
Q

Do PP2As have the same targets as Cyclin-Cdks?

A

yes

91
Q

What type of feedback loop exists between PP2A and M-Cdk?

A

participate in a complex feedback loop that regulates their activities

92
Q

What is the role of PP2A before M-phase?

A

PP2A is active and dephosphorylates M-Cdk targets to stop progression into mitosis

93
Q

What happens during M-phase regarding M-Cdk and M-cyclin?

A
  • M-cyclin is produced
  • making M-Cdk active and directly inhibiting PP2A activity
  • M-Cdk phosphorylates its targets to promote mitosis progression
94
Q

What is the function of Cdk inhibitor proteins (CKIs)?

A

bind to Cyclin-Cdks, disrupting their interaction and inactivating the Cdk

95
Q

Name two examples of Cdk inhibitor proteins (CKIs).

A
  • p27
  • p21
96
Q

What is the role of inhibitory phosphorylation in Cyclin-CDK regulation?

A

occurs at a different site from the activating phosphate added by Cdk-activating kinase (CAK)

97
Q

Which kinase is responsible for adding inhibitory phosphorylation to Cyclin-CDKs?

A

Wee1 kinase

98
Q

What is the function of Cdc25 phosphatase in Cyclin-CDK regulation?

A
  • can remove the inhibitory phosphorylation from Cyclin-CDKs
  • activating it
99
Q

How does active M-Cdk contribute to its own activation?

A

Active M-Cdk activates its activators, including the phosphorylation of Cdc25, and inhibits its inhibitors, such as PP2A phosphatase and Wee1 kinase

100
Q

What is the significance of positive feedback loops in Cyclin-CDK activation?

A

ensure robust Cyclin-CDK activation, creating an “all or nothing” choice to proceed with the cell cycle

101
Q

What happens when M-Cdk is active in terms of its inhibitors?

A

Active M-Cdk inhibits its inhibitors

102
Q

What is the relationship between Cdc25 phosphatase and M-Cdk?

A

can activate M-Cdk by removing its inhibitory phosphorylation

103
Q

What role do mitogens or growth factors have in Cyclin-Cdk regulation?

A

provide a “green light” for progression

104
Q

What does the presence of a favorable extracellular environment indicate?

A

green light

105
Q

What are some cell conditions that inhibit Cyclin-Cdk activity?

A
  • DNA damage
  • unreplicated DNA
  • chromosome unattached to spindle
106
Q

What is the role of E2F in the cell cycle?

A

a transcription factor required for S-phase gene expression

107
Q

How does Rb (Retinoblastoma protein) regulate E2F?

A

Rb binds to and inhibits E2F, preventing it from activating the transcription of S-phase gene

108
Q

What can inhibit Rb and lead to cell cycle progression?

A

by phosphorylation, which allows E2F to become active and promote S-phase gene expression

109
Q

What are mitogens and what is their role in the cell cycle?

A
  • extracellular signaling molecules that stimulate cell division
  • They activate signaling pathways that lead to the production of cell cycle control proteins
110
Q

Describe the signaling pathway activated by mitogens.

A
  • Mitogens activate receptor tyrosine kinases (RTKs)
  • which then activate Ras and a MAP kinase cascade
  • ultimately leading to the upregulation of Myc expression
111
Q

What is the significance of Myc in cell cycle control?

A

a key transcription factor that promotes the expression of G1-cyclins

112
Q

What happens if Rb is always inactive?

A

E2F remains active, leading to uncontrolled transcription

113
Q

What is the role of Myc in the cell cycle?

A

activates G1-cyclin gene expression

114
Q

How does G1-Cdk affect Rb?

A

phosphorylates Rb (Retinoblastoma protein), leading to its inactivation

115
Q

What happens when Rb is phosphorylated?

A

releases E2F, a transcription factor that activates the expression of S-phase genes

116
Q

What feedback mechanisms are involved in E2F activation?

A

Positive feedback occurs through E2F autoactivation and phosphorylation of Rb by G1/S-Cdk and S-Cdk,

117
Q

How does DNA damage affect the cell cycle?

A

induces the activation of the p53 transcription factor,

118
Q

What is the role of p53 in response to DNA damage?

A

activates the expression of p21

119
Q

What is p21 and how does it function?

A

a cyclin-dependent kinase inhibitor (CKI) that inhibits G1/S-Cdk and S-Cdk, providing a “red light” signal that gives the cell a chance to fix DNA damage before progressing

BIO230 Final (5 decks)

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