PI3K inhibitors Flashcards
What is the general substrate of PI3K
phosphatidyl-inositol
Where can the inositol head group be phosphorylated
3,4,5 free OH groups
Which OH groups cannot be phosphorylated on the inositol head group of PI
Positions 2 and 6
Nor 1 because it’s already bound to the phosphate group linking it to the DAG lipid anchor
What determines where a phosphorylated PtdIns will localise intracellularly?
The positions in which it is phosphorylated
How does PI3P concentration change in response to growth factor stimulation
Doesn’t change, considered to be constitutive lipid
How do PIP3 and PI(3,4)P2 concentrations change after growth factor stimulation
Levels of the lipids rise rapidly following growth factor stimulation
what is the result of a PtdIns being phosphorylated at the 3-OH position?
It’s no longer a substrate for phospholipase
What kind of proteins do PIP3 and PI(3,4)P2 bind to
Proteins with a plextrin homology domain which is found in protein kinases, adaptor proteins and regulators of small GTPases
What protein domains do PI(3)P bind to? and where are these found?
FYVE - Mostly in proteins involved in membrane trafficking
PX - in proteins that regulate NADPH oxidase complex, endocytic trafficking
What are the four members of the class I PI3K isoforms
p110alpha/PIK3CA, p110beta/delta/gamma
What are the 3 members of the class II PI3Ks
C2alpha, C2beta, C2gamma
What is the class III PI3K
vps34
What is the substrate of the class I PI3Ks and what do they produce from it
PI(4,5)P2 is the substrate and it forms PIP3
How does PIP3 bind to downstream protein substrates
Via the proteins PH domain
What is the substrate of class II/III PI3Ks
PI and converts it to PI(3)P which binds its target proteins by FYVE and PX domains.