4: Cell Cycle and Signaling Flashcards
Briefly Summarise the overall events that happen from Growth factor bindin to receptor to change in gene expressions that trigger mitosis
- Mitogenic Growth Factor binds to Growth Factor receptor
- Dimerisation of Receptor causes activation of tyrosine kinase
- Tyrosine Kinase recruits receptor and adaptor proteins (e.g G-protein RAS)
- Adaptor Proteins set off Kinase cascase
- KInase cascade causes change in gene expression and activates mitotic proteins
What is the result of phosphorylation of the intracellular tyrosine caused by dimerisation of the Growth factor receptor after Growth factor binding?
Phosphorylation of thyrosine caused by dimerisation of the growth factor receptor provides docking sites for adapter proteins
What are adaptor proteins?
Proteins that bind to the phosphorylated Thyrosine Kinase in at the receptor membrane and assist in further signal transduction
What are tha characteristics of adaptor proteins and what is their function?
They tend to facilitate binding between different proteins instead of having an enzymatic function itself (but can have enzymatic function) –> bring proteins together (protein-protein interactions)
Thereofre they are
- modular –> many protein-binding molecules and domains (structural and functional units that can be seen in many other molecules)
What kind of protein is Grb2?
What is its function?
Growth factor receptor-bound protein 2 is an adaptor protein
Explain the structure and function of Gbr2
Is an adaptor protein–> brings proteins together
- It has three domains
- SH2 domain bindin to the phosphorylated tyrosine of GFR
- 2 SH3 domains bindig to other molecules
- proline-rich regions of other molecules
Explain the role of Grb2 in the activation of RAS
The exchange factor SOS binds to the SH3 domain of Grb2 and is activated by it
- SOS exchanges GDP bound to RAS to GTP and thereby activates it
How does RAS get activated and inactivated?
Activation
- GDP is replaced by GTP (done by exchange factors e.g. SOS)
Inactivation
- by GAP (GTPase activating protiens) that turn GTP to GDP again
What are possible oncogenic mutations in the RAS gene?
Why are they oncogenic?
Mutations can lead to permanent onswitch of RAS –> no inactivation possible
- e.g. mutation prevents GAP binding –> no inactivation
- e..g Mutation prevents GTP hydrolysis
What is the effects of an activated RAS protein?
it activates a protein kinase cascade
more specifically: Extracellular signal-regulated kinase (ERK) cascade
What is the name of the intracellular kinase cascades that induce mitosis?
- Generally
- ACtivated by RAS
- Gneral Name= Mitogen-activated protein kinase (MAPK) cascades
- RAS activates (or extracellular binding) Extracellular signal-regulated kinase (ERK) cascade
What is the Name of the different tyrosine Kinases that are activated in the ERK cascade?
- Kinase
- RAF
- Kinase
- MEK
- Kinase
- ERK
Explain the involvement of the ERK cascade in the formation of cancer
B-Raf is an oncogene - mutationally activated in melanomas
What does activation of the ERK cascase (or other kinase cascades) lead to?
- Change in protein activity
- Change in gene expression
What are Cdks?
When are they present in the cell?
How are they regulated?
Cyclin-dependent kinases
- always present in human cells but
- only activated with cyclins and phosphorylation