Signalling Mechanisms in Growth and Division Flashcards
What transcription factor is stimulated by growth factor signalling and is vital to starting the cell cycle?
c-Myc
Give an example of an anti-cancer drug that targets tyrosine kinase receptors.
Herceptin – inhibits the Her2 tyrosine kinase receptor (important in many tumours e.g. breast)
Broadly speaking, how might Ras signalling be different in cancer?
Ras could be permanently switched on (in the GTP bound form), thus it constantly signals cell division
What is the family that the ERK cascade belongs to called?
MAPK cascade (Mitogen-activated protein kinase cascade)
What are the three kinases involved in the ERK cascade?
Raf
MEK
ERK
What important gene is turned on by the kinase cascade?
c-Myc
What type of kinase are cyclin-dependent kinases (Cdks)?
Serine-threonine kinases
What conditions do Cdks require to become activated?
Binding to cyclin
Phosphorylation (activating phosphorylation and removal of inhibitory phosphorylation)
What does the mitosis-promoting factor (MPF) consist of?
Cdk1 + cyclin B
What are the requirements, in terms of phosphorylation, for MPF to become active?
Cdk activating kinase (CAK) adds an activating phosphate and Wee1 adds an inhibitory phosphate at the same time
Cdc25 then removes the inhibitory phosphate
What activates MPF at the end of interphase?
Removal of the inhibitory phosphorylation by Cdc25
Describe the positive feedback loop that is formed by MPF activation.
Removal of the inhibitory phosphorylation by Cdc25 produces active MPF, which then phosphorylates Cdc25 and increases its activity meaning that more MPF can be activated
Which Cdk/cyclin is required for G1/S phase?
Cdk2-cyclin E
Which Cdk/cyclin is required for S phase?
Cdk2-cyclin A
How can the same Cdk be used for two different stages?
Cyclin binding alters the substrate specificity of Cdk
Also, different substrates are available at different stages of the cell cycle
What is one of the most important transcription targets of c-Myc?
Cyclin D
What is the first Cdk/cyclin complex that is formed when a cell goes from G0 to G1?
Cdk4/6-cyclin D