CPPS 325 VERGE 2025 Signalling #12 to upload (1)

Question 1

What is the primary role of the PI 3-kinase/Akt pathway?

Answer 1

Promotes cell survival

This pathway is critical for regulating apoptosis and cell growth.

Question 2

How is PI 3-kinase activated?

Answer 2

By binding to specific phospho-tyrosines on activated RTKs

RTKs refer to receptor tyrosine kinases.

Question 3

What does Akt (also known as PKB) do in the PI 3-kinase pathway?

Answer 3

Phosphorylates proteins that regulate apoptosis

Question 4

What is the function of FOXO in the context of the PI 3-kinase/Akt pathway?

Answer 4

Regulates transcription of death genes

FOXO proteins are transcription factors that can promote cell death when not phosphorylated.

Question 5

What is the role of mTOR in the Akt signaling pathway?

Answer 5

Phosphorylates Akt for full activation

Question 6

What are cytokines?

Answer 6

Soluble proteins or peptides that mediate interactions between cells

Question 7

What are the three types of effects that cytokines can have?

Answer 7

Autocrine, paracrine, and endocrine effects

Question 8

What is the key pathway activated by cytokine signaling?

Answer 8

JAK/STAT pathway

Question 9

Who are the key players in the JAK/STAT pathway?

Answer 9

JAKs and STATs

Question 10

What are JAKs?

Answer 10

Non-receptor tyrosine kinases that phosphorylate receptors

Question 11

What is the function of STATs in the JAK/STAT pathway?

Answer 11

Transcription factors that become activated upon phosphorylation

Question 12

How does the activation of JAK lead to the activation of STAT?

Answer 12

By phosphorylating tyrosine residues on the receptor

Question 13

What happens to phosphorylated FOXO in the cytoplasm?

Answer 13

It is sequestered by 14-3-3 protein and cannot enter the nucleus

Question 14

Fill in the blank: The mTOR pathway is a central regulator of _______.

Answer 14

cell growth

Question 15

What is the main take-home message regarding the PI-3K survival pathway in cancer treatment?

Answer 15

Target and antagonize the PI-3K survival pathway of cancer cells

Question 16

What is the significance of BKM120 in cancer therapy?

Answer 16

It is a PI-3K inhibitor used to induce apoptosis in cancer cells

Question 17

True or False: Cytokine signaling has a more direct link to transcriptional regulation than MAPK.

Answer 17

True

Question 18

What does the PI3K pathway activation indicate in breast cancer?

Answer 18

It is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer

Question 19

What are the two subunits of PI 3-kinase?

Answer 19

Regulatory subunit (p85) and catalytic subunit (p110)

Question 20

What does the phosphorylation of Akt lead to?

Answer 20

Activation of various target proteins involved in cell survival

Question 21

What is the role of pleckstrin homology (PH) domains in the PI 3-kinase pathway?

Answer 21

They facilitate the interaction of target proteins with PIP3

Question 22

What happens when the PI-3-kinase signaling system is switched off?

Answer 22

Phosphorylated FOXO can be dephosphorylated and re-enter the nucleus

Question 23

What is the mechanism of action for erythropoietin (Epo)?

Answer 23

Requires both the Epo receptor and JAK2 for erythrocyte development

Question 24

What are the functional domains of STAT proteins?

Answer 24

SH2 domain for recognizing phospho-tyrosines

Question 25

What are the essential components for the development of erythrocytes?

Answer 25

Erythropoietin receptor (EpoR) and JAK2 ## Footnote These components are crucial for erythropoiesis.

Question 26

Cytokine receptor signaling shares features with which type of signaling?

Answer 26

RTK signaling ## Footnote RTK stands for Receptor Tyrosine Kinase.

Question 27

What is a common feature shared by RTK and cytokine receptor signaling?

Answer 27

Blocking loop (activation lip) ## Footnote This feature is important for the regulation of signaling pathways.

Question 28

What is the first step in the activation of Janus kinase (JAK)?

Answer 28

Ligand binds to receptor and receptor dimerizes ## Footnote This dimerization brings JAKs close to each other for activation.

Question 29

What happens after Janus kinase becomes activated?

Answer 29

Janus kinase phosphorylates several tyrosine residues on the cytosolic domain ## Footnote This phosphorylation is crucial for downstream signaling.

Question 30

What does inactive monomeric STAT bind to?

Answer 30

Phosphotyrosine via SH2 domain ## Footnote This binding is necessary for STAT activation.

Question 31

What is the role of dimerized STAT in the signaling pathway?

Answer 31

Translocate to nucleus and regulate transcription ## Footnote This includes transcribing suppressors of cytokine signaling.

Question 32

How is the JAK-STAT pathway negatively regulated in the short term?

Answer 32

By phosphatases (SHPs) ## Footnote These phosphatases dephosphorylate signaling proteins to terminate the signal.

Question 33

What is one method of long-term regulation of the JAK-STAT pathway?

Answer 33

Suppressors of Cytokine Signaling (SOCS) family ## Footnote SOCS are involved in a regulatory feedback loop.

Question 34

What does the SH2 domain of inactive SHP1 associate with?

Answer 34

The tyrosine that was phosphorylated by activated JAK2 ## Footnote This association allows SHP1 to dephosphorylate JAK2.

Question 35

How do dimerized phosphorylated STATs affect gene expression?

Answer 35

They regulate gene expression including SOCS ## Footnote This is part of a negative feedback mechanism.

Question 36

What happens when SOCS bind to receptors?

Answer 36

Blocks catalytic domain and/or binding of signaling molecules ## Footnote This prevents further signaling through the JAK-STAT pathway.

Question 37

What happens to receptors tagged with ubiquitin?

Answer 37

Targeted for degradation ## Footnote This process helps to regulate the duration of signaling.

Question 38

Fill in the blank: Eero Mäntyranta had primary familial and congenital _______ due to a mutation in the erythropoietin receptor gene.

Answer 38

polycythemia ## Footnote This condition leads to an increased red blood cell mass and hemoglobin.

Question 39

What effect does the mutation in the erythropoietin receptor have on oxygen carrying capacity?

Answer 39

Increase of up to 50% ## Footnote This enhances the blood's ability to carry oxygen.

Question 40

True or False: Eero Mäntyranta could bind STAT5 but could not bind SHP-1 phosphatase.

Answer 40

True ## Footnote This inability to bind SHP-1 impacts signal termination.