Signal transduction Flashcards
Describe FRET signals
Interacting up to 10nm away
Depend on distance of flurophores
Strong FRET = 2 non interacting proteins, targeted to mem by lipid tether
NO FRET= 2 non interacting p in the cytosol
What is PKB activated by ?
Insulin and growth factors
What does PKB do?
Forced membrane localisation drives cell transformation
Cytosolic PKB = signalling or oncogenic mem bound forms of PKB/AKT
What are 3 ways of controlling protein localisation at the membrane ?
- Portein interaction
- Lipid interaction motifs
- Lipid tether
What are the motifs for protein interactions in localisation?
Phosphobinding motifs: SH2, PTB
Ubiquitin binding motifs
AKAP interaction domains (cytosol and mem b protein interact)
What are the motifs for lipid interaction motif in localisation?
Phosphoionositide interacting motifs: PH, FYVE, PHD+ lysine
DAG:C2
mem interacting : C1
What are the motifs for tether binding in localisation?
Myristoylation
Prenylation
What is myristoylation?
Fatty acylation- covalent addition of palmitic or myristic FA to protein
to n-terminal lysine residue
Irreversible
What is co-translational myristoylation ?
N-terminal methionine removed
CoA activates myristic acid
Myristic acid couples to glycine
What are the 6 steps of post translational myristoylation: APOPTOSIS?
- glysine exposed by caspase cleavage of Bid
- Bid myristoylated
- lipid tether = insert into mito mem
- Recruit BAK to mito mem
- Cytochrome C release
- Downstream apoptosis
What are the membrane domains which help when a lipid tether is not enough to stabilise mem localisation ?
- Phosphoinositide interaction domain
2. Another tether
What is Kras?
Highly mutated Targeted to PM by interacting its poly basic region with phospoinositides - Ras= mutations in 12,13,14 - KRas= phosphoswitch controlled Apoptosis GTP dependent
What is progeria syndrome ?
Abnormal processing of CAAX protein prelamin A
Treated with FTase inhibitors
