Cell signalling 3 Flashcards
What does Raf use to phosphorylate and activate Mek?
ATP
What does activated Mek do?
It phosphorylates and activated Erk
What does Mek use to phosphorylate and activate Erk?
ATP
What can activated Erk do?
Phosphorylate, and thus activate different proteins and transcription factors
What can the proteins and transcription factors activated by Erk do?
Promote cell proliferation
How is amplification occuring at each stage of the MAP kinase cascade
Each kinase can activate multiple kinases etc etc
How could an issue with a kinase pathway lead to cancer?
If the pathway was permanently activated, all steps including the activation of proteins and transcription factors involved in cell proliferation would go on unmitigated–> uncontrollable cell division
What is an oncogene?
A muated gene that has the potential to cause cancer
What is a proto-oncogene?
Unmutated genes which affect cell proliferation (and could turn into oncogenes if mutated)
Why could the Ras genes and the MAPK genes be considered proto-oncogenes?
They are both eventually involved in cell proliferation, and could mutate
How is phosphorylation status a signalling switch?
The phosphorylated form of some proteins is the active form, while the dephosphorylated form is the inactive form
What catalyses the turning off of a phosphorylated, activated protein?
Protein phosphotase
Where does PI3kinase bind to in the PI3K pathway?
The phosphotyrosine onto HER3
What happens to PI3K after it docks onto the phosphotyrosine on HER3?
It is activated
What type of kinase is PI3K?
A lipid kinase
What does PI3K uses PIP2 for?
As a substrate to generate PIP3
Where are PIP2 and PIP3 found?
Membrane bound
What do some protein regions of proteins such as protein kinase 1 and Akt allow?
High affinity binding to PIPs
What are the domains that allow certain proteins to bind to PIPs?
Pleckstrin Homology Domains
What do Protein kinase 1 and Akt use PIP3 as?
A docking site, allowing them to be brought to the plasma membrane
What does protein kinase 1 do to Akt once they are both at the plasma membrane?
It phosphorylates, and activates it
What does Akt do immediately after being phosphorylated?
It dissociates from the PIP and the plasma membrane
What process is Akt important in?
Cell survival
What is active Akt?
A serine/threonine kinase
What does active Akt do to Bad?
Akt phosphorylates Bad
What does Bad do in its active form?
It holds Bcl2 in its inactive state
What does the phosphorylation of Bad do?
Changes Bad’s conformation, causing it to release Bcl2
What does the release of Bcl2 from bad to to Bcl2?
Activates it
What is the role of active Bcl2
Promotion of cell survival by inhibition of apoptosis
How does active Akt mediate cell growth?
Through other signalling events, it ends up activating mTor
What does mTor do once activated?
Inhibits protein degradation and stimulates protein synthesis
Where does phospholipase C gamma bind to?
A phosphotyrosine of HER3
What does phospholipase C gamma use PIP2 for?
As a substrate to generate DAG (diacyl glycerol) and IP3 (inositol triphosphate)
Where is IP3 sent after it is generated?
To the cytosol
What does IP3 do once it is in the cytosol?
It binds to, and opens calcium channels in the ER
What is the direct effect of IP3 binding to Ca2+ channels on the ER?
The cytosolic concentration of Ca2+ increases
What does DAG do once generated?
Recruits and activates protein kinase C (PKC)
What can cytosolic ca2+ bind to?
PKC
