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Cell Signalling > Ser-Thr Kinase Pathway > Flashcards

Ser-Thr Kinase Pathway Flashcards

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1
Q

What is the general function of Serine/Threonine kinases?

A

Phosphorylate the hydroxyl groups of serine or threonine residues in target proteins.

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2
Q

Name two well-known Serine/Threonine kinases.

A

Protein kinase A (PKA) and Protein kinase C (PKC).

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3
Q

What is the role of Protein Kinase A (PKA)?

A

PKA regulates various cellular processes by phosphorylating target proteins in response to cAMP levels.

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4
Q

How is Protein Kinase C (PKC) activated?

A

PKC is activated by diacylglycerol (DAG) and calcium ions.

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4
Q

Which second messenger activates PKA?

A

Cyclic AMP (cAMP).

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5
Q

What type of kinases are MAP kinases (Mitogen-Activated Protein Kinases)?

A

Serine/Threonine kinases.

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6
Q

How are Ser/Thr kinases involved in the regulation of the cell cycle?

A

Cyclin-dependent kinases (CDKs), which are Ser/Thr kinases, control progression through the cell cycle by phosphorylating key regulatory proteins.

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7
Q

What is the role of TGF-β receptor kinases?

A

They phosphorylate target proteins involved in cell growth, differentiation, and immune regulation.

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8
Q

What is the substrate specificity of Serine/Threonine kinases?

A

They specifically phosphorylate the hydroxyl group of serine or threonine residues in proteins.

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9
Q

Which Serine/Threonine kinase is important in the insulin signaling pathway?

A

Akt (Protein kinase B, PKB).

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9
Q

What is the role of mTOR in the cell?`

A

mTOR regulates cell growth, proliferation, and metabolism in response to nutrient availability.

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9
Q

What are the main domains in a typical Ser/Thr kinase?

A

A catalytic domain and a regulatory domain.

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10
Q

Which kinase pathway is activated by growth factors and controls cell survival?

A

The PI3K/Akt/mTOR pathway.

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11
Q

Which enzyme deactivates Serine/Threonine kinases by dephosphorylation?

A

Protein phosphatases.

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11
Q

What is the role of AMP-activated protein kinase (AMPK)?

A

AMPK is a cellular energy sensor that regulates metabolic pathways in response to low energy levels.

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12
Q

What is the role of CaMK (Calcium/Calmodulin-dependent protein kinases)?

A

CaMKs mediate calcium signaling and regulate functions like memory and muscle contraction.

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13
Q

What signaling pathway is Smad proteins associated with, and which type of kinase activates them?

A

The TGF-β signaling pathway; activated by Serine/Threonine kinases (TGF-β receptors).

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14
Q

What kinase is involved in the activation of the transcription factor NF-κB?

A

IκB kinase (IKK), a Serine/Threonine kinase.

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15
Q

Which Serine/Threonine kinase regulates glycogen synthesis?

A

Glycogen synthase kinase-3 (GSK-3).

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15
Q

What role does Akt/PKB play in glucose metabolism?

A

Akt promotes glucose uptake by stimulating GLUT4 translocation to the plasma membrane.

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16
Q

Which Serine/Threonine kinase is involved in the stress-activated MAPK pathway?

A

p38 MAP kinase.

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17
Q

What is the role of the tumor suppressor protein PTEN in the PI3K/Akt pathway?

A

PTEN dephosphorylates PIP3, inhibiting Akt activation and thus opposing the PI3K/Akt pathway.

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17
Q

What is the effect of phosphorylation by CDKs on cell cycle proteins?

A

It either activates or inhibits their function, controlling cell cycle progression.

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18
Q

How is Protein Kinase A (PKA) regulated?

A

By cAMP levels, which bind to the regulatory subunits of PKA, releasing and activating the catalytic subunits.

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19
Q

Which kinase is responsible for phosphorylating the eukaryotic initiation factor eIF4E-binding protein (4E-BP1)?

A

mTOR, which regulates protein synthesis through 4E-BP1 phosphorylation.

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20
Q

What role do Ser/Thr kinases play in apoptosis regulation?

A

Kinases like Akt inhibit apoptosis by phosphorylating and inactivating pro-apoptotic proteins (e.g., Bad).

20
Q

What is the function of RSK (Ribosomal S6 Kinase)?

A

RSK phosphorylates substrates involved in cell growth, survival, and proliferation, downstream of the MAPK/ERK pathway.

21
Q

What is the significance of the LKB1/AMPK pathway in metabolic regulation?

A

It senses energy status and switches cells from anabolic to catabolic processes under low energy conditions.

22
Q

Which kinase family plays a critical role in the innate immune response by activating pro-inflammatory signaling pathways?

A

IKK (IκB kinase) family, which activates NF-κB.

23
Q

Which Ser/Thr kinase is involved in synaptic plasticity and memory formation?

A

CaMKII (Calcium/Calmodulin-dependent kinase II).

24
Q

What is the role of Raf in the MAPK/ERK signaling pathway?

A

Raf is a Ser/Thr kinase that activates the MAPK/ERK pathway by phosphorylating MEK (MAPK/ERK kinase).

25
Q

What is the primary function of the Smad proteins in TGF-β signaling?

A

Smad proteins, when phosphorylated by TGF-β receptor kinases, regulate transcription of target genes involved in growth inhibition and differentiation.

26
Q

How do Ser/Thr kinases participate in DNA damage response?

A

Kinases like Chk1 and Chk2 phosphorylate and activate proteins involved in DNA repair, cell cycle arrest, and apoptosis following DNA damage.

27
Q

What happens when the Ser/Thr kinase GSK-3 is phosphorylated?

A

Phosphorylation of GSK-3 at a specific inhibitory site reduces its activity, leading to increased glycogen synthesis and other effects.

28
Q

What is the role of Aurora kinases in the cell cycle?

A

Aurora kinases are Ser/Thr kinases that regulate key events in mitosis, such as chromosome segregation and cytokinesis.

29
Q

How does the phosphorylation state of a substrate affect its activity?

A

Phosphorylation can either activate or inhibit the substrate’s function, depending on the context and the specific phosphorylation site.

30
Q

Which Ser/Thr kinase phosphorylates Hsp27 (Heat shock protein 27) in response to stress?

A

MAPKAPK-2 (MAPK-activated protein kinase 2).

30
Q

What is the role of the kinase ATM in the cell?

A

ATM (Ataxia-Telangiectasia Mutated) is a Ser/Thr kinase that responds to DNA damage by phosphorylating proteins involved in DNA repair and cell cycle control.

30
Q

How do mutations in Ser/Thr kinases contribute to disease?

A

Mutations can lead to aberrant kinase activity, resulting in diseases like cancer (e.g., B-Raf mutations in melanoma).

31
Q

What role do CDKs (Cyclin-dependent kinases) play in cancer?

A

Dysregulated CDK activity can lead to uncontrolled cell proliferation, contributing to cancer development.

32
Q

What is the role of the kinase mTOR in autophagy regulation?

A

mTOR inhibits autophagy under nutrient-rich conditions by phosphorylating components of the autophagy machinery.

33
Q

What is the role of the kinase PAK in cytoskeletal regulation?

A

PAK (p21-activated kinase) is a Ser/Thr kinase that regulates actin cytoskeleton dynamics, affecting cell motility and morphology.

34
Q

Which enzyme class opposes the action of Serine/Threonine kinases?

A

Protein phosphatases, which remove phosphate groups from phosphorylated serine/threonine residues.

35
Q

Which Ser/Thr kinase is involved in the inflammatory response by regulating IL-1 signaling?

A

TAK1 (TGF-β activated kinase 1).

35
Q

How do Ser/Thr kinases regulate transcription?

A

By phosphorylating transcription factors (e.g., CREB, Myc), Ser/Thr kinases modulate gene expression.

35
Q

Which Ser/Thr kinase family is involved in regulating the actin cytoskeleton and cell motility?

A

ROCK (Rho-associated kinase) family.

36
Q

SMAD is a?

A

Transcription factor

37
Q

Transcription factors are present in ?

A

Bothy cytosol and Nucleus

38
Q

Receptor Types?

A

Type 1 and Type 2

39
Q

Ligands bind at?

A

Type 2

40
Q

Type 2 recruits?

A

Type 1

41
Q

Type 2 Phosphorylates?

A

Type 1

42
Q

After Phosphorylation, Type 1 becomes?

A

Docking site

43
Q

Type 2 develop docking site by?

A

Itself

44
Q

At docking sit?

A

SMAD binds through C-terminal, and this leads to conformational changes in SMAD , and MH1 site get exposed.

44
Q

what binds at MH1 site?

A

Importin Beta

45
Q

Once MH1 get exposed, it allows SMAD to form?

A

SMAD Complex

46
Q

SMAD complex moves to?

A

Nucleus

47
Q

In Nucleus, SMAD act as a ?

A

transcription factor

48
Q

TGF-Beta stimulates cells to produce?

A
  1. Extracellular Matrix protein (Collagen, fibronectin & proteoglycans)
  2. Cytokines and Growth factors
  3. Inhibitors for Cell cycle progression (eg: p21 and
    p27, which cause cell cycle arrest)
  4. Pro-fibrotic molecule
  5. Epithelial to Mesenchymal transition markers
49
Q

The word “SMAD” comes from?

A

SMA : C.elegans (TGF-beta is similar to SMA)
D is Decapentaplegic: DPP genein drosophilla

50
Q

Oher ligands are?

A

TGF-beta
Activin
Inhibin
BMP-Bone morphogenic protein

51
Q

Termination is done by?

A
  1. Dephosphorylation by Phosphatases
  2. Ubiquitination and Proteasomal Degradation
  3. Feedback Inhibition
  4. Sequestration or Inactivation of Kinases
  5. Receptor Internalization and Degradation
  6. Inhibition by Natural Inhibitors
  7. Downregulation of Second Messengers
  8. Negative Regulation by Phosphatase-Tensin Homolog (PTEN)
  9. Reactive Oxygen Species (ROS) and Cellular Stress

Cell Signalling (8 decks)

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