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Molekylær cellebiologi > Cell signaling III > Flashcards

Cell signaling III Flashcards

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1
Q

What are enzyme-coupled receptors?

A

Transmembrane proteins with a ligand-binding domain on the outer surface of the plasma membrane and a cytosolic domain that has intrinsic enzyme activity or associates with an enzyme.

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2
Q

How many transmembrane segments do GPCRs have compared to enzyme-coupled receptors?

A

GPCRs have seven transmembrane segments; enzyme-coupled receptors typically have only one.

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3
Q

What is the primary function of receptor tyrosine kinases (RTKs)?

A

To phosphorylate themselves and create phosphotyrosine docking sites for intracellular signaling proteins.

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4
Q

What is the mechanism of activation for receptor tyrosine kinases?

A

Ligand binding brings two receptors together to activate their cytoplasmic kinase domains.

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5
Q

What are some examples of signal proteins that act via RTKs?

A
  • Epidermal growth factor (EGF)
  • Insulin
  • Insulin-like growth factor (IGF1)
  • Nerve growth factor (NGF)
  • Platelet-derived growth factor (PDGF)
  • Macrophage-colony-stimulating factor (MCSF)
  • Fibroblast growth factor (FGF)
  • Vascular endothelial growth factor (VEGF)
  • Ephrin
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6
Q

What is transautophosphorylation in the context of RTKs?

A

The process where dimerized RTKs phosphorylate each other, activating their kinase domains.

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7
Q

What role do phosphorylated tyrosines on RTKs serve?

A

They create docking sites for intracellular signaling proteins.

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8
Q

What is the function of insulin receptor substrate-1 (IRS1) in insulin receptor signaling?

A

IRS1 binds to specific phosphorylated tyrosines on the activated receptor and is phosphorylated at multiple sites, creating additional docking sites.

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9
Q

What are SH2 domains?

A

Phosphotyrosine-binding domains that allow proteins to bind to activated RTKs.

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10
Q

What is the effect of binding to phosphotyrosines on signaling proteins?

A

It may activate the protein either through phosphorylation or by inducing a conformational change.

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11
Q

What is the primary role of the cytoplasmic tyrosine kinase Src in RTK signaling?

A

To phosphorylate other signaling proteins on tyrosines.

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12
Q

What happens to RTKs after they are phosphorylated by activated kinases?

A

They create high-affinity docking sites for specific intracellular signaling proteins.

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13
Q

What is the significance of the tyrosine kinase domain in RTKs?

A

It is responsible for the phosphorylation of tyrosines that create docking sites for signaling proteins.

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14
Q

What is the role of phosphotyrosines in receptor tyrosine kinases (RTKs)?

A

Phosphotyrosines form docking sites that bind different signaling proteins.

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15
Q

How do activated RTKs signal to the cell body from the axon?

A

They are endocytosed with bound signaling proteins and transported along the axon.

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16
Q

What is the main function of Ras in RTK signaling?

A

Ras relays signals from RTKs to downstream signaling pathways.

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17
Q

What is the consequence of hyperactive mutant forms of Ras?

A

They contribute to uncontrolled proliferation of cancer cells.

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18
Q

What two classes of signaling proteins regulate Ras activity?

A
  • Ras guanine nucleotide exchange factors (Ras GEFs)
  • Ras GTPase-activating proteins (Ras GAPs)
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19
Q

What is the role of Ras GEFs?

A

They stimulate the dissociation of GDP and promote the binding of GTP to activate Ras.

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20
Q

How do RTKs normally activate Ras?

A

By activating a Ras GEF or inhibiting a Ras GAP.

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21
Q

What is the name of the Ras GEF discovered in Drosophila?

A

Son-of-sevenless (Sos).

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22
Q

What is the MAP kinase signaling module composed of?

A
  • MAP kinase kinase kinase (MAPKKK)
  • MAP kinase kinase (MAPKK)
  • MAP kinase (MAPK)
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23
Q

Name the three components of the mammalian Ras–MAP kinase signaling pathway.

A
  • Raf (MAPKKK)
  • Mek (MAPKK)
  • Erk (MAPK)
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24
Q

What is the function of Erk in the MAP kinase pathway?

A

Erk phosphorylates various proteins, including transcription regulators.

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25
What role does MAP kinase play in cell signaling?
MAP kinase activates a complex positive feedback loop to produce an all-or-none, irreversible response.
26
What mechanisms influence the duration and features of signaling responses?
Positive and negative feedback loops.
27
What does the negative feedback loop in the Ras–MAP-kinase pathway involve?
Erk phosphorylates and inactivates Raf.
28
What do Rho family GTPases regulate?
Actin and microtubule cytoskeletons, cell shape, polarity, motility, adhesion, cell-cycle progression, gene transcription, and membrane transport.
29
Name the three best-characterized members of the Rho family.
* Rho * Rac * Cdc42
30
What is the role of PI 3-kinase in RTK signaling?
It phosphorylates inositol phospholipids to create lipid docking sites in the plasma membrane.
31
What is the significance of PI(3,4,5)P3 in cell signaling?
It serves as a docking site for various intracellular signaling proteins.
32
What are PH domains?
Protein–protein interaction domains that bind to PI(3,4,5)P3.
33
What is the primary role of the Akt protein in signaling?
It promotes cell survival and growth.
34
How do Rho GEFs and GAPs function in relation to Rho family GTPases?
GEFs activate and GAPs inactivate Rho family GTPases.
35
What is the primary function of PTEN in relation to PI 3-kinase signaling?
PTEN dephosphorylates PI(3,4,5)P3, regulating the signaling pathway.
36
What cellular response does the activation of RhoA lead to?
It stimulates myosin-dependent contraction of the actin cytoskeleton.
37
What type of receptors can activate PI 3-kinase?
Both RTKs and GPCRs.
38
What is the major pathway activated by the hormone insulin?
The PI-3-kinase–Akt signaling pathway ## Footnote This pathway is crucial for promoting survival and growth of many cell types.
39
What type of protein kinase is Akt also known as?
Protein kinase B (PKB) ## Footnote Akt is a serine/threonine protein kinase.
40
What do members of the insulin-like growth factor (IGF) family stimulate in animal cells?
Survival and growth ## Footnote They bind to specific receptor tyrosine kinases (RTKs).
41
Which molecule recruits Akt and PDK1 to the plasma membrane?
PI(3,4,5)P3 ## Footnote This molecule is produced by PI 3-kinase.
42
What is the effect of Akt on most of its target proteins?
Inactivation ## Footnote This action ultimately promotes cell survival and growth.
43
What is mTOR and what role does it play in cell growth?
mTOR is a protein kinase that regulates cell growth ## Footnote It exists in two complexes: mTORC1 and mTORC2.
44
What are the two main complexes of mTOR and their functions?
* mTORC1: Stimulates cell growth and is sensitive to rapamycin * mTORC2: Promotes cell survival and activates Akt ## Footnote mTORC2 is insensitive to rapamycin.
45
What activates mTORC1?
* Growth factors * Nutrients such as amino acids ## Footnote These activators promote cell growth.
46
What is the role of Src family kinases?
They phosphorylate overlapping but distinct sets of intracellular signaling proteins ## Footnote Members include Src, Yes, Fgr, Fyn, Lck, and others.
47
What is the main function of integrins in cell signaling?
They bind to the extracellular matrix and activate intracellular signaling pathways ## Footnote Integrins help trigger the assembly of cell-matrix junctions called focal adhesions.
48
What is the JAK–STAT signaling pathway associated with?
Cytokine receptors ## Footnote It involves Janus kinases (JAKs) and signal transducers and activators of transcription (STATs).
49
What happens when cytokine binding occurs with cytokine receptors?
Two JAKs come into close proximity and phosphorylate each other ## Footnote This increases the activity of their tyrosine kinase domains.
50
What is the role of JAKs in the JAK–STAT signaling pathway?
JAKs phosphorylate each other and tyrosines on cytokine receptors, creating phosphotyrosine docking sites for STATs.
51
What happens to STATs after they are phosphorylated by JAKs?
Phosphorylated STATs dissociate from the receptor and form dimers.
52
What is the function of activated STAT dimers in the nucleus?
They bind to specific cis-regulatory sequences in genes to stimulate transcription.
53
What is the TGFβ superfamily?
A large number of structurally related, secreted, dimeric proteins that regulate various biological functions.
54
How does TGFβ signaling begin?
A TGFβ dimer interacts with two type-I and two type-II receptors.
55
What is the primary function of receptor tyrosine kinases (RTKs)?
To dimerize and activate their kinase domains upon ligand binding.
56
What is the role of PI 3-kinase in signaling pathways?
It phosphorylates specific phosphoinositides to create lipid docking sites for signaling proteins.
57
What is a key function of the monomeric GTPase Ras?
To activate a three-component MAP kinase signaling module.
58
What is the role of the Notch protein in gene regulation?
It acts as a latent transcription regulator involved in cell-fate choices and regulating pattern formation ## Footnote Notch signaling is crucial during animal development, particularly in the production of neural cells.
59
Define lateral inhibition in the context of Notch signaling.
A process where a precursor cell signals its neighbors not to adopt the same fate, influencing cell differentiation ## Footnote This is crucial for preventing excess neural cells from forming.
60
What activates the Notch protein and leads to transcription of Notch-response genes?
Binding of Delta to the Notch receptor initiates proteolytic cleavage and translocation of the Notch tail to the nucleus ## Footnote This process converts a transcription repressor into a transcription activator.
61
What is unique about the activation of the Notch protein compared to most receptors?
Its activation is irreversible; once activated, Notch cannot be reused ## Footnote This is due to the nature of its proteolytic cleavage.
62
What are Wnt proteins and their primary function?
Secreted signaling molecules that control various aspects of animal development ## Footnote They are involved in pathways like the Wnt/β-catenin signaling pathway.
63
How do Wnt proteins interact with their receptors?
They bind to Frizzled and LDL-receptor-related protein (LRP) to form a co-receptor dimer ## Footnote This interaction stabilizes β-catenin and prevents its degradation.
64
What happens to β-catenin in the absence of a Wnt signal?
β-catenin interacts with a degradation complex containing APC, axin, GSK3, and CK1, leading to its phosphorylation and degradation ## Footnote This process keeps Wnt-responsive genes inactive.
65
What are the three Hedgehog proteins identified in vertebrates?
* Sonic * Desert * Indian hedgehog ## Footnote These proteins are crucial for signaling in development.
66
What is the primary role of the primary cilium in Hedgehog signaling?
The primary cilium serves as an antenna for the extracellular Hedgehog signal ## Footnote Most signaling proteins of the Hedgehog pathway are located within the primary cilium.
67
What is the function of the Patched receptor in Hedgehog signaling?
Patched inhibits Smoothened and regulates the activity of Gli transcription regulators ## Footnote Its activity is inhibited when Hedgehog ligand binds to it.
68
What does the binding of Hedgehog to Patched promote?
The transport of Patched out of the cilium and the activation of Smoothened ## Footnote This leads to increased expression of Hedgehog target genes.
69
What are NFκB proteins essential for?
They are central to many inflammatory and innate immune responses ## Footnote They also play roles in normal animal development.
70
How is NFκB activated in response to TNFα?
Through a signaling pathway that leads to the phosphorylation and degradation of IκB proteins ## Footnote This release allows NFκB to translocate to the nucleus.
71
What types of receptors activate the NFκB signaling pathway?
* Toll receptors * Toll-like receptors * TNF receptors * IL1 receptors ## Footnote All activate NFκB via similar mechanisms.
72
What is the function of IκB proteins in relation to NFκB?
IκB proteins bind to NFκB dimers and keep them in an inactive state in the cytoplasm ## Footnote This prevents NFκB from activating gene transcription.
73
What is the role of nuclear receptors?
They are ligand-modulated transcription regulators that bind small, hydrophobic signal molecules ## Footnote Examples include steroid hormones and thyroid hormones.
74
What happens when nuclear receptors bind their ligands?
They alter the ability of the receptors to control the transcription of specific genes ## Footnote This serves as both receptor and effector for the signal.
75
What does activated NFκB stimulate?
The transcription of the IkBa gene ## Footnote The protein product of IkBa acts to sequester and inhibit NFκB in the cytoplasm.
76
What are steroid hormones made from?
Cholesterol ## Footnote Examples include cortisol and sex hormones.
77
What role does cortisol play in the body?
Influences the metabolism of many types of cells ## Footnote It is produced in the cortex of the adrenal glands.
78
How is vitamin D synthesized?
In the skin in response to sunlight ## Footnote It regulates Ca2+ metabolism after being converted to its active form.
79
What is the function of thyroid hormones?
Increase the metabolic rate of many cell types ## Footnote They are made from the amino acid tyrosine.
80
What is the mechanism of action for nuclear receptors?
Bind to specific DNA sequences adjacent to the genes they regulate ## Footnote They can be inactive or active depending on ligand binding.
81
What is a circadian clock?
An internal rhythm that regulates behaviors at different times of day ## Footnote This includes metabolic enzyme activities and sleep-wake cycles.
82
What is the primary function of circadian clocks?
To anticipate regular daily changes in the environment ## Footnote They must be reset by external cues like light.
83
Where are circadian clocks located in multicellular organisms?
In individual cells ## Footnote In humans, they are found in specialized cells of the suprachiasmatic nucleus (SCN) of the hypothalamus.
84
What is the role of SCN cells?
They regulate diurnal cycles of sleeping, waking, and hormone release ## Footnote They receive neural cues from the retina to entrain to the light-dark cycle.
85
What is the delayed negative feedback loop in circadian clocks?
Accumulation of certain gene products switches off their own transcription with a delay ## Footnote This causes cells to oscillate between states of product presence and absence.
86
What resets the circadian clock in Drosophila?
Light sensed by intracellular flavoproteins called cryptochromes ## Footnote These associate with the Tim protein and cause its degradation.
87
What types of signal molecules can diffuse across the plasma membrane and activate intracellular receptors?
Small, hydrophobic signal molecules such as steroid and thyroid hormones ## Footnote These molecules directly regulate the transcription of specific genes.
88
What mechanism produces 24-hour oscillations in transcription regulators?
Delayed negative feedback ## Footnote This mechanism anticipates the cell’s changing needs during day and night.

Molekylær cellebiologi (11 decks)

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