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
main phospholipid classes
phosphoglycerides
sphingomyelin
under phosphoglycerides we have?
Ptd Ser
PtdE tn
PtdCho
PtdIns
there are also glycolipid classe which is?
glucosyl-cerebroside
lipids containing insitol?
Phosphatidylinositol 4,5-bisphosphate (PIP2)
phoospholipase C converts Phosphatidylinositol 4,5-bisphosphate to what?
diacyl glycerol (DAG)
i’ll do this variety of PIPS i signalling later because I don’t understand it.
but if you guys get it please do it.
PIP IN MEMBRANE RECRUITS SIGNALLING PROTEINS ( don’t understand it yet as well)
where do these target (1)?
PtdIns(3,4)P2
PtdIns(3,5)P2
PtdIns(4,5)P2
PtdIns(3,4,5)P3
PtdIns(3,4)P2 ————PH
PtdIns(3,5)P2 ————none identified
PtdIns(4,5)P2 —————-PH, FERM, ANTH, ENTH, tubby (PX?),
AP2-, plus several cytoskeletal proteins
PtdIns(3,4,5)P3————–PH
where do these target (2)?
PtdIns(3)P
PtdIns(4)P
PtdIns(5)P
PtdIns(3)P————–FYVE, PX (PH?)
PtdIns(4)P ————-PH (OSBP/SAPP/CERT), EpsinR AP1 σ1
PtdIns(5)P—————none identified
