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Signaling pathways Flashcards

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1
Q

What enzyme is activated by the Gs protein in the cAMP pathway?

A

Adenylate cyclase

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2
Q

What reaction does adenylate cyclase catalyze?

A

Conversion of ATP into cAMP

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3
Q

What role does cAMP play inside the cell?

A

It acts as a second messenger that diffuses freely in the cytoplasm.

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4
Q

What is the main target of cAMP?

A

Protein kinase A (PKA).

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5
Q

What happens when PKA is activated?

A

It phosphorylates various target proteins, including ion channels.

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6
Q

How does phosphorylation affect ion channels?

A

t can either open or close ion channels depending on the channel type.

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7
Q

How does PKA contribute to signal amplification?

A

One PKA molecule can phosphorylate multiple target proteins.

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8
Q

What enzyme terminates the cAMP signal?

A

Phosphodiesterase, which breaks down cAMP.

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9
Q

How does this signaling pathway (cAMP/PKA) influence gene transcription?

A

Activated PKA phosphorylates the transcription factor CREB.

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10
Q

After phosphorylation, what does CREB do?

A

Binds to CBP (CREB-binding protein), activating RNA polymerase II.

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11
Q

What genes does RNA polymerase II transcribe in this context?

A

Genes containing CRE (cAMP response elements) in their promoters.

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12
Q

Which protein activates phospholipase C (PLC) in the other main GPCR pathway?

A

The Gq protein.

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13
Q

What molecule does phospholipase C cleave?

A

Phosphatidylinositol-4,5-bisphosphate (PIP2).

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14
Q

What two second messengers are produced from PIP2 cleavage?

A

Diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3).

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15
Q

Where does DAG act, and what does it activate?

A

DAG remains in the membrane and activates protein kinase C (PKC).

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16
Q

What is the role of PKC once activated?

A

It phosphorylates target proteins affecting metabolism, receptor function, and ion channels.

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17
Q

Where does IP3 go after formation?

A

It diffuses freely into the cytosol.

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18
Q

What is the main target of IP3?

A

The IP3 receptor on the smooth endoplasmic reticulum (SER)

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19
Q

What happens when IP3 binds to its receptor?

A

Calcium channels on the SER open, releasing Ca²⁺ into the cytosol.

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20
Q

Why is the increase in intracellular Ca²⁺ important?

A

It triggers various cellular effects depending on the cell type.

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21
Q

What calcium-binding protein in neurons senses this Ca²⁺ increase?

A

Calmodulin (CaM).

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22
Q

Which enzyme does CaM activate after binding calcium?

A

Calcium/calmodulin-dependent protein kinase II (CaMKII).

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23
Q

What functions do CaMKII and other calcium-sensitive proteins have?

A

They modulate membrane permeability and regulate gene expression.

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24
Q

Besides regulating enzymes, how else can activated G proteins influence ion channels?

A

The βγ subunit complex can bind directly to ion channels, increasing their ion permeability

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25
Q: What type of kinases are MAP kinases?
A: Serine/threonine-specific protein kinases.
26
What stimuli activate MAP kinases?
Mitogens, osmotic stress, heat shock, and pro-inflammatory cytokines.
27
What cellular processes do MAP kinases regulate?
Gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.
28
How are receptor tyrosine kinases (RTKs) involved in MAP kinase activation?
Activated RTKs recruit adaptor proteins that form complexes linking the receptor to downstream signaling proteins.
29
What is Ras and what family does it belong to?
Ras is a small GTP-binding protein; it is a monomeric GTPase.
30
How does Ras switch from inactive to active?
Ras exchanges GDP for GTP upon activation by an activating protein.
31
What is the order of kinases in the MAP kinase phosphorylation cascade?
Ras → MAP kinase kinase kinase (MAP3K) → MAP kinase kinase (MAP2K) → MAP kinase (MAPK).
32
What is the effect of activated MAP kinase on the nucleus?
MAP kinase phosphorylates gene regulatory proteins, altering gene transcription.
33
What cellular outcomes can MAP kinase activation lead to?
Cell proliferation, survival, or differentiation.
34
Why is the MAP kinase pathway important in cancer?
Mutations causing aberrant(diverging from normal type) MAP kinase activation can lead to uncontrolled cell growth and tumor formation.
35
What type of receptors use serine/threonine kinases to directly regulate gene expression?
TGF-β superfamily receptors.
36
What proteins do activated TGF-β receptors phosphorylate?
SMAD proteins.
37
What happens to phosphorylated SMADs?
They form complexes and enter the nucleus to regulate gene transcription.
38
What role does the NF-κB pathway play?
It regulates stress responses, inflammation, and innate immunity.
39
How is NF-κB activated?
Via receptors like Toll-like receptors, TNFα, and IL-1, which lead to phosphorylation and degradation of IκB, freeing NF-κB to enter the nucleus.
40
Q: What is the JAK/STAT signaling pathway used for?
A: Direct control of gene expression, especially in immune responses (e.g., interferons).
41
How do JAKs activate STAT proteins?
JAKs phosphorylate STATs, which then dimerize and translocate to the nucleus to regulate gene expression.
42
Name some negative regulators of the JAK/STAT pathway.
SOCS proteins, protein tyrosine phosphatases (PTPs), and PIAS proteins.
43
What type of receptors use serine/threonine kinases for direct signaling?
Receptors phosphorylated on serine/threonine residues, activated by extracellular signals.
44
Which proteins are directly phosphorylated and activated by serine/threonine kinase receptors?
SMAD proteins.
45
What superfamily of hormones activates serine/threonine kinase receptors?
The TGF-β (transforming growth factor-beta) superfamily.
46
What happens to SMAD proteins after phosphorylation?
They dissociate from the receptor, bind other SMADs to form complexes, and move to the nucleus.
47
What is the role of SMAD complexes in the nucleus?
They stimulate transcription of specific target genes.
48
Which cellular processes are regulated by the TGF-β signaling pathway?
Cell growth, differentiation, apoptosis, homeostasis, and essential functions in development and adults.
49
What cellular roles does the NF-κB signaling pathway play?
Stress responses, inflammation, and innate immunity.
50
Which receptors activate the NF-κB pathway?
Toll-like receptors, TNFα receptors, and IL-1 receptors.
51
What is the structural form of TNFα and its receptors?
Both exist as trimers.
52
What happens when TNFα binds to its receptor?
It causes rearrangement of cytosolic receptor tails, recruiting signaling proteins and activating a serine/threonine kinase.
53
What is IκB kinase (IKK) composed of?
Two kinase subunits (IKKα and IKKβ) and a regulatory subunit called NEMO.
54
How is NF-κB kept inactive in the cytoplasm?
By binding to the inhibitory protein IκB.
55
What role does activated IKKβ play in NF-κB activation?
It phosphorylates IκB, leading to IκB ubiquitination and degradation.
56
What happens after IκB is degraded?
NF-κB is released and translocates into the nucleus.
57
What does NF-κB do in the nucleus?
It stimulates transcription of target genes, often with coactivator proteins.
58
What happens to the ~45 kDa Sonic hedgehog protein right after it is translated?
It undergoes autocatalytic cleavage into a ~20 kDa N-terminal signaling domain and a ~25 kDa C-terminal domain.
59
What special modification happens to the N-terminal signaling domain during cleavage?
A cholesterol molecule is attached to its C-terminus.
60
Why is this cholesterol modification important? In SHH pathway
It helps the signaling domain get secreted, trafficked properly, and interact with receptors.
61
How can Sonic hedgehog signal to cells?
Both autocrine (to the cell that produces it) and paracrine (to neighboring cells via secretion).
62
Which protein is involved in helping Sonic hedgehog get secreted for paracrine signaling?
Dispatched protein (DISP).
63
When Sonic hedgehog reaches a target cell, what does it bind to?
The Patched-1 (PTCH1) receptor.
64
What is the state of Smoothened (SMO) when Sonic hedgehog is absent?
PTCH1 inhibits SMO, preventing downstream signaling.
65
What happens to SMO when Sonic hedgehog binds to PTCH1?
SMO inhibition is removed, allowing it to activate downstream pathways.
66
Which transcription factors are activated after SMO activation?
GLI transcription factors.
67
What do activated GLI proteins do in the nucleus?
They regulate the transcription of genes targeted by the hedgehog signaling pathway.
68
In vertebrate limb development, where is Sonic hedgehog produced?
In a small region called the zone of polarizing activity (ZPA) at the posterior edge of the limb bud.
69
How does Sonic hedgehog influence digit formation in limbs?
The concentration and exposure duration of Sonic hedgehog determine digit identity.
70
In a different pathway, what kind of cell communication involves the Delta ligand and Notch receptor?
Contact-dependent signaling between neighboring cells.
71
What process does the contact-dependent pathway regulate through lateral inhibition?
It ensures neighboring cells develop into different cell types (e.g., nerve vs epithelial cells).
72
When a precursor cell becomes a nerve cell, what does it do to neighbors?
It sends Delta ligand signals to neighboring cells to prevent them from becoming nerve cells. instead they become epithelial cells
73
Where does the first cleavage of the Notch receptor occur?
Inside the trans-Golgi network, producing the mature receptor on the cell surface.
74
What triggers the subsequent cleavages of the Notch receptor?
Binding of Delta ligand from a neighboring cell.
75
What is released after these cleavages?
The Notch intracellular domain (NICD).
76
What does NICD do after release?
It travels into the nucleus.
77
Which nuclear protein does NICD bind?
RBP-Jκ.
78
What effect does NICD binding have on RBP-Jκ?
Converts it from a transcriptional repressor into an activator.
79
What is the final outcome of NICD binding to RBP-Jκ?
Activation of Notch-responsive gene transcription.

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