Kinases as molecular targets Flashcards
________ of proteins and lipids are important for proliferation, secretion and apoptosis
phosphorylation
what catalyses phosphorylation and dephosphorylation
phosp: kinases
dephosp: phosphates
changes in levels and activities of kinases effect what?
normal cell function and maintenance of homeostasis
what do we want to do to kinases in anti cancer therapy?
small molecule kinase inhibitors
protein kinases catalyse the transfer of what?
the terminal phosphate of ATP to substrates that contain a serine, threonine or tyrosine residues
where can lipids be phosphorylated?
plans and organelle membranes
How do kinase inhibitors work? competitive?
competitive and mimcic the hydrogen bonds that are normally formed by the adenine ring of ATP and the kinase
type 1 kinase inhibitors?
recognise the active conformation of the kinase
type 2 kinase inhibitors?
recognise the inactive conformation of the kinase
how do allosteric inhibitors work?
bind at a site outside the atp binding site and modulate activity
allosteric inhibitors are ______. explain
selective- particular to particular kinases
how do covalent inhibitors work? bind to active site or allosteric?
form an irreversible, covalent bond to the kinase active site, most frequently by reacting with a nucleophilic cysteine residue
what happens when a ligand bind to a TKR?
the TK monomers in the membrane dimerise which activates TK activity
what happens to TKRs which have a cancer mutation? 3. different scenarios
- always found in the dimeric form- don’t need a signal to respond to.
- over expression of the receptor- clustered on surface which become dimers and activate irrespective of ligand binding.
- GF expression increased– autocrine signalling
what is the activation of TKRs on cancer cells by GF upregulation called?
autocrine signalling
