CPPS 325 VERGE 2025 Signalling #12 to upload (1) Flashcards
What is the primary role of the PI 3-kinase/Akt pathway?
Promotes cell survival
This pathway is critical for regulating apoptosis and cell growth.
How is PI 3-kinase activated?
By binding to specific phospho-tyrosines on activated RTKs
RTKs refer to receptor tyrosine kinases.
What does Akt (also known as PKB) do in the PI 3-kinase pathway?
Phosphorylates proteins that regulate apoptosis
What is the function of FOXO in the context of the PI 3-kinase/Akt pathway?
Regulates transcription of death genes
FOXO proteins are transcription factors that can promote cell death when not phosphorylated.
What is the role of mTOR in the Akt signaling pathway?
Phosphorylates Akt for full activation
What are cytokines?
Soluble proteins or peptides that mediate interactions between cells
What are the three types of effects that cytokines can have?
Autocrine, paracrine, and endocrine effects
What is the key pathway activated by cytokine signaling?
JAK/STAT pathway
Who are the key players in the JAK/STAT pathway?
JAKs and STATs
What are JAKs?
Non-receptor tyrosine kinases that phosphorylate receptors
What is the function of STATs in the JAK/STAT pathway?
Transcription factors that become activated upon phosphorylation
How does the activation of JAK lead to the activation of STAT?
By phosphorylating tyrosine residues on the receptor
What happens to phosphorylated FOXO in the cytoplasm?
It is sequestered by 14-3-3 protein and cannot enter the nucleus
Fill in the blank: The mTOR pathway is a central regulator of _______.
cell growth
What is the main take-home message regarding the PI-3K survival pathway in cancer treatment?
Target and antagonize the PI-3K survival pathway of cancer cells
What is the significance of BKM120 in cancer therapy?
It is a PI-3K inhibitor used to induce apoptosis in cancer cells
True or False: Cytokine signaling has a more direct link to transcriptional regulation than MAPK.
True
What does the PI3K pathway activation indicate in breast cancer?
It is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer
What are the two subunits of PI 3-kinase?
Regulatory subunit (p85) and catalytic subunit (p110)
What does the phosphorylation of Akt lead to?
Activation of various target proteins involved in cell survival
What is the role of pleckstrin homology (PH) domains in the PI 3-kinase pathway?
They facilitate the interaction of target proteins with PIP3
What happens when the PI-3-kinase signaling system is switched off?
Phosphorylated FOXO can be dephosphorylated and re-enter the nucleus
What is the mechanism of action for erythropoietin (Epo)?
Requires both the Epo receptor and JAK2 for erythrocyte development
What are the functional domains of STAT proteins?
SH2 domain for recognizing phospho-tyrosines
What are the essential components for the development of erythrocytes?
Erythropoietin receptor (EpoR) and JAK2
These components are crucial for erythropoiesis.
Cytokine receptor signaling shares features with which type of signaling?
RTK signaling
RTK stands for Receptor Tyrosine Kinase.
What is a common feature shared by RTK and cytokine receptor signaling?
Blocking loop (activation lip)
This feature is important for the regulation of signaling pathways.
What is the first step in the activation of Janus kinase (JAK)?
Ligand binds to receptor and receptor dimerizes
This dimerization brings JAKs close to each other for activation.
What happens after Janus kinase becomes activated?
Janus kinase phosphorylates several tyrosine residues on the cytosolic domain
This phosphorylation is crucial for downstream signaling.
What does inactive monomeric STAT bind to?
Phosphotyrosine via SH2 domain
This binding is necessary for STAT activation.
What is the role of dimerized STAT in the signaling pathway?
Translocate to nucleus and regulate transcription
This includes transcribing suppressors of cytokine signaling.
How is the JAK-STAT pathway negatively regulated in the short term?
By phosphatases (SHPs)
These phosphatases dephosphorylate signaling proteins to terminate the signal.
What is one method of long-term regulation of the JAK-STAT pathway?
Suppressors of Cytokine Signaling (SOCS) family
SOCS are involved in a regulatory feedback loop.
What does the SH2 domain of inactive SHP1 associate with?
The tyrosine that was phosphorylated by activated JAK2
This association allows SHP1 to dephosphorylate JAK2.
How do dimerized phosphorylated STATs affect gene expression?
They regulate gene expression including SOCS
This is part of a negative feedback mechanism.
What happens when SOCS bind to receptors?
Blocks catalytic domain and/or binding of signaling molecules
This prevents further signaling through the JAK-STAT pathway.
What happens to receptors tagged with ubiquitin?
Targeted for degradation
This process helps to regulate the duration of signaling.
Fill in the blank: Eero Mäntyranta had primary familial and congenital _______ due to a mutation in the erythropoietin receptor gene.
polycythemia
This condition leads to an increased red blood cell mass and hemoglobin.
What effect does the mutation in the erythropoietin receptor have on oxygen carrying capacity?
Increase of up to 50%
This enhances the blood’s ability to carry oxygen.
True or False: Eero Mäntyranta could bind STAT5 but could not bind SHP-1 phosphatase.
True
This inability to bind SHP-1 impacts signal termination.
