intracellular kinase signalling Flashcards
describe Ras link to MAPK signal cascade
Ras-GTP activates a variety of responses via MAP kinase cascade:
what is this MAP kinase cascade?
1) Initial activation (often by phosphorylation) of a protein kinase, mitogen-activated protein kinase kinase kinase (MAPKKK), which phosphorylates & activates a
2) second class of kinase, MAP kinase kinase (MAPKK), which phosphorylates & activates a
3) third class of kinase, MAPK; which then phosphorylates and alters the activity of target proteins, e.g. transcription factors.
MAPKKKs and MAPKs are ____________ kinases; MAPKKs are ___________________ kinases.
MAPKKKs and MAPKs are serine/threonine kinases; MAPKKs are threonine/tyrosine kinases.
MAP Kinase pathway involving Ras
MAPKKK = Raf
MAPKK = MEK1/MEK2 (MAP/ERK kinase)
MAPK = ERK (extracellular signal regulated kinase).
A major target of ERK is _______________(__________-).
A major target of ERK is RSK (ribosomal S6 kinase).
Scaffolds organise __________________-
Scaffolds organise multiprotein signalling complexes
scaffolds Targets ________________
scaffolds Targets MEK/ERK to specific substrates and facilitates communication with other pathways
scaffolds Regulates the ______________
scaffolds Regulates the kinetics, amplitude and localisation of MEK/ERK signalling, for specific biological response.
describe cross-talk
when Many kinases within these cascades can phosphorylate proteins outside of their cascade system:
what does cross-talk between the different cascades
Could lead to a lack of specificity of response, but degree of cross-talk is limited by the scaffold proteins that determine which substrate proteins are within the vicinity of the kinases.
__________ is one of the genes most commonly mutated in human tumours
Ras – one of the genes most commonly mutated in human tumours
Mammalian cells – 3 Ras proteins namely
H-, K-, N-ras
Mammalian cells – 3 Ras proteins
cycles between what?
Cycle between GTP and GDP forms
what is the common mutation in human tumours in Ras
loss of GTP-hydrolysing ability
Common mutation in human tumours is loss of GTP-hydrolysing ability in Ras
this leads to?
Ras trapped in “on” position
Continually stimulates cell proliferation
New signal transduction inhibitor drugs block ______________________
New signal transduction inhibitor drugs block nodes in the pathway, e.g. Raf kinase inhibitors
