Cell signaling II Flashcards

(58 cards)

1
Q

What are G-protein-coupled receptors (GPCRs)?

A

The largest family of cell-surface receptors that mediate responses to external signals, hormones, neurotransmitters, and local mediators.

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2
Q

How many GPCRs are estimated to be present in humans?

A

More than 800 GPCRs.

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3
Q

What types of signal molecules can activate GPCRs?

A

Proteins, small peptides, derivatives of amino acids and fatty acids, photons of light, and molecules that can be smelled or tasted.

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4
Q

How many different GPCRs can a single signal molecule activate?

A

For example, epinephrine activates at least 9 distinct GPCRs.

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5
Q

What is the structural characteristic of GPCRs?

A

They consist of a single polypeptide chain that threads across the lipid bilayer seven times.

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6
Q

What is the role of G proteins in GPCR signaling?

A

They relay the signal into the cell interior.

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7
Q

What are the components of heterotrimeric G proteins?

A

Three subunits: α, β, and γ.

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8
Q

What happens to the α subunit of a G protein when a GPCR is activated?

A

It releases GDP and binds GTP.

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9
Q

What effect does GTP binding have on the Gα subunit?

A

It triggers a conformational change, allowing it to dissociate from the receptor and Gβγ pair.

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10
Q

What is the function of RGS proteins?

A

They act as GTPase-activating proteins (GAPs) that enhance GTP hydrolysis and shut off G-protein-mediated responses.

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11
Q

What does cyclic AMP (cAMP) act as in signaling pathways?

A

A second messenger.

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12
Q

What enzyme synthesizes cyclic AMP from ATP?

A

Adenylyl cyclase.

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13
Q

How is cyclic AMP degraded?

A

By cyclic AMP phosphodiesterases.

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14
Q

What does the activation of Gs G protein do to cAMP levels?

A

It increases cAMP concentrations.

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15
Q

What is the role of protein kinase A (PKA) in cAMP signaling?

A

It phosphorylates specific serines or threonines on target proteins, regulating their activity.

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16
Q

What happens to PKA upon cAMP binding?

A

The regulatory subunits dissociate, activating the catalytic subunits.

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17
Q

What are A-kinase anchoring proteins (AKAPs)?

A

Proteins that bind to the regulatory subunits of PKA and to components of the cytoskeleton or organelle membranes, localizing the kinase inside the cell.

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18
Q

What is the role of cyclic AMP in activating PKA?

A

Binding of cAMP to regulatory subunits induces a conformational change, activating the catalytic subunits.

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19
Q

What does the cyclic AMP response element (CRE) do?

A

It is a short cis-regulatory sequence that is recognized by the CRE-binding (CREB) protein, activating gene transcription.

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20
Q

What is the function of CREB in response to cAMP?

A

CREB is phosphorylated by PKA, which then recruits CBP to stimulate transcription of target genes.

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21
Q

What are the two products generated from the hydrolysis of PI(4,5)P2 by phospholipase C-β?

A
  • Inositol 1,4,5-trisphosphate (IP3)
  • Diacylglycerol.
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22
Q

What effect does IP3 have in the cell?

A

It binds to IP3 receptors in the ER membrane, triggering the release of Ca2+ into the cytosol.

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23
Q

What is the role of diacylglycerol (DAG) in cell signaling?

A

It activates protein kinase C (PKC) and remains embedded in the plasma membrane.

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24
Q

What is the function of protein kinase C (PKC)?

A

PKC phosphorylates target proteins, influencing various cellular responses.

25
What triggers the release of Ca2+ from the endoplasmic reticulum (ER)?
The binding of IP3 to IP3 receptors.
26
What is the concentration gradient of Ca2+ across the plasma membrane?
Ca2+ concentration is low in the cytosol and high in the extracellular fluid and ER.
27
What mechanism is responsible for the termination of the Ca2+ signal?
Ca2+-pumps in the plasma membrane and ER membrane pump Ca2+ out of the cytosol.
28
What happens when Ca2+ channels in the plasma membrane are activated?
Ca2+ influx from outside the cell occurs.
29
What is the primary function of Ca2+ in muscle cells?
To trigger contraction.
30
What is one example of a response activated by GPCRs through PLCβ?
Glycogen breakdown in the liver by vasopressin.
31
What is the role of the Na+-driven Ca2+ exchanger in muscle and nerve cells?
It couples the efflux of Ca2+ to the influx of Na+ ## Footnote This mechanism aids in the rapid signaling processes in these cells.
32
What do Ca2+ puffs or sparks represent in a cell?
Local opening of small numbers of IP3 receptors in the ER membrane ## Footnote These puffs occur when cytosolic IP3 concentrations are low.
33
How does an increase in extracellular signal strength affect Ca2+ release?
It raises IP3 concentrations, activating more IP3 receptors and spreading Ca2+ release ## Footnote This can result in regenerative waves of Ca2+ release throughout the cytosol.
34
What is calmodulin's role in Ca2+ signaling?
It acts as a multipurpose intracellular Ca2+ receptor regulating many Ca2+-regulated processes ## Footnote Calmodulin can constitute as much as 1% of a cell's total protein mass.
35
How does calmodulin change upon binding Ca2+?
It undergoes an activating conformational change ## Footnote Two or more Ca2+ ions must bind for this change to occur.
36
What is one function of Ca2+/calmodulin in the cell?
Activating various target proteins and enzymes ## Footnote This includes activating the plasma membrane Ca2+-pump to help restore resting Ca2+ levels.
37
What is CaM-kinase II and where is it primarily found?
A Ca2+/calmodulin-dependent protein kinase found in most animal cells, especially enriched in the nervous system ## Footnote It can constitute up to 2% of total protein mass in certain brain regions.
38
What is one example of a transcription regulator phosphorylated by CaM-kinases?
CREB protein ## Footnote This phosphorylation can activate or inhibit the transcription of specific genes.
39
How do cells sense the frequency of Ca2+ spikes?
Through Ca2+-sensitive proteins that change their activity based on spike frequency ## Footnote This allows for different cellular responses to varying Ca2+ signaling patterns.
40
What happens when Ca2+/calmodulin binds to the regulatory segment of a kinase?
The kinase becomes active ## Footnote This binding prevents the regulatory segment from inhibiting the kinase domain.
41
What is autophosphorylation in the context of CaM-kinase II?
Phosphorylation of adjacent kinase subunits by each other ## Footnote Autophosphorylation further activates the enzyme and prolongs its activity.
42
How does CaM-kinase II serve as a molecular memory device?
It remains active after the Ca2+ signal decays ## Footnote This occurs because autophosphorylation allows the kinase to maintain activity without continuous Ca2+ presence.
43
What is the role of protein phosphatase in regulating CaM-kinase II?
Removes autophosphorylation ## Footnote This action shuts off the kinase activity, resetting its function.
44
What do cyclic-nucleotide-gated ion channels play a role in?
Smell and vision ## Footnote These channels are crucial for signal transduction in sensory pathways.
45
How do olfactory receptors detect odors?
By increasing cAMP levels ## Footnote They activate a specific G protein called Golf, which stimulates adenylyl cyclase.
46
What is the function of rhodopsin in vision?
It activates a G protein called transducin ## Footnote This activation leads to a cascade that decreases cyclic GMP levels, closing cation channels.
47
What is the function of nitric oxide (NO) in blood vessels?
NO relaxes smooth muscle in the walls of blood vessels, causing vessel dilation.
48
What triggers the synthesis of nitric oxide in endothelial cells?
Acetylcholine stimulates NO synthesis by activating a GPCR on the endothelial cell membranes.
49
What is the role of nitric oxide synthases (NOS) in NO production?
NOS catalyzes the deamination of the amino acid arginine to produce NO.
50
What are the three general modes of adaptation for GPCRs?
* Receptor inactivation * Receptor sequestration * Receptor destruction
51
How does receptor inactivation affect GPCR signaling?
Receptor inactivation alters the receptor so it can no longer interact with G proteins.
52
What is the function of arrestin in GPCR signaling?
Arrestin prevents activated receptors from interacting with G proteins and helps couple the receptor to endocytosis machinery.
53
What is the amplification effect in signaling pathways involving GPCRs?
A single activated receptor can trigger the activation of multiple G proteins, leading to significant increases in second messenger concentrations.
54
What is the primary function of cyclic GMP in smooth muscle cells?
It triggers relaxation of smooth muscle cells.
55
What do GPCRs indirectly activate or inactivate?
Plasma-membrane-bound enzymes or ion channels ## Footnote GPCRs act through G proteins to influence these targets.
56
What is the function of GPCR kinases (GRKs)?
They phosphorylate only activated receptors ## Footnote GRKs are activated by the GPCR they phosphorylate.
57
What happens to activated GPCRs when the extracellular signal is removed?
They are inactivated by phosphorylation and association with arrestins ## Footnote This process turns off the signaling pathway rapidly.
58
What is the effect of GPCR signaling cascades on target protein molecules?
They amplify the responses, changing many thousands of target protein molecules ## Footnote This occurs for each molecule of extracellular signaling ligand bound.