Mapk Pathways Flashcards
What are the 3 main mapk in humans
P38 a-d , jnk 1-4, erk 1/2
What are the mapkk in all 3 mapk pathways in humans
Mek 1-7
Which Mek mapkk is shared by jnk and p38
Mek 4
What type of responses does erk do
Proliferation, diff, development , survival, migration
What are the 4 major signals for erk pathway via grb2 activation via sh2 etc
Egf (egfr)
Pdgf (pdgfr)
Insulin (ir)
Ngf (ngfr)
What is pdgf signalling for
Wound healing
What is ngf signalling for
Growth of neurones
What other 2 mapkk activate / phosphorylate erk
Mos and tpl2
What is mos for
Activates both p38 and erk to induce nfkb production which is a tf for things like survival
What does tpl2 do
Regulation of tumours via erk
What cytoplasmic effect does erk have
Pla2 phospholipase a2 production which allows formation of arachidonic acid which used to produce pge2 etc
Which 2 tf are activated as nuclear targets of erk and why
C Fos and c myc
C fos (ap 1 tf)
What does c myc do
Control elongation in txn
What things does c fos ap1 regulate
Genes for pro, differentiation, apoptosis
Which 2 phosphatases de phosphorylate erk
Ptp- sl (Dephos phosphotyrosine residues)
Dusps (dephos tyrosine, thr and ser residues)
What treatments have been targeting erk pathway for cancer
Receptor mutation treatment
Ras blocking to membrane
Raf inhibitors
Mek inhibitors
Combination (eg Mek and raf inhibitors)
What melanoma treatment was used to target erk
Raf inhibitor
What are the main issues in erk cancer treatment
Relapse
What are the major signals for p38 pathway
Osmotic stress, cytokines eg il1, death receptors, oxidative stress
What are the 5 mapkkk in p38 path
Mekk 1-4, ask1, dlk
What is ask1 mapkkk for
Apoptosis response via p38
What is dlk mapkkk for
Neurodegeneration control
What are the 2 main mapkk in p38 pathway
Mkk 3,6
Which Isoform of p38 is the only one that has mapkk mkk 4 instead of 3 or 6
P38 alpha
How are the 4 p38 isoforms produced
Differential RNA splicing
Give examples of p38 action
Inflammation, proliferation, diff, apoptosis , RNA splicing , senescence
Which effectors of p38 phosphorylate creb and histones
Msk 1/2
What do mk 2/3 do which are effectors of p38
Regulate gene exp
How do p38 isofomrs differ
Different cell targets
What dephos p38 for control
Protein phosphatases 1 and 2
Which p38s are in all tissue
A and b
Which p38 is only in skeletal muscles
Y gamma
Where is delta p38 expressed
Pancreas, intestine, heart, kidney etc
Where is p38 phosphorylsted by mkk 3,4 or 6
Tyrosine residues in TGY motif
Thr,glycine, tyr
What response would occur if phos of p38 was sustained or short
Sustained is apoptosis
Fast phos is growth/proliferation via gf
How many mapk paths in yeast cerevisiae
4
Which mapk is for the pheromone response for mating
Fus3
Which mapk is for filamentation or incase growth (activated by starvation)
Kss1
Why is there a lot of potential cross talk between fus3 mating and invasive growth/dilamentstikn of kss1
Same mapkkk and mapkk
Ste11 and ste7
Which scaffold protein holds fus3 ste11 and 7 to stop it cross talking with kss1 and allows mating
Ste5
What is the stress induced mapk in cerevisiae , candida and Pom be
Hog1
Does hog1 have a scaffold
Yes pbs2 which also acts as a mapkk for ste11 (yes hog shares mapkkk of fus3 and kss1)
Which 2 scaffolds does erk have
Ksr and mp1
What is always bound to ksr scaffold
Mek and raf, erk only associates if signal produced
What protein allows mp1 localisation in endosomes to allow it to activate erk path
P14
Which signal is mp1 important for
Egf which is pro and diff
Is mek bound to mp1 always
Yes
How many branches of mapkkk does hog1 in cerevisiae have before the pbs2 and hog1
2 (the ste11 one and another )
How does hog help osmotic stress
Glycerol transport
What other responses does hog mediate
Cell cycle progession , txn , translation, metabolism, ion transport
Which mapk is important for candida virulence so the path is good for drug target
Hog1
What is the 2 component system of hog in candida
The phos of 3 proteins - ( histidine pk, phosphotransfer protein , response regulator)
Inactivates hog phos
This phos is blocked when signals like osmotic stress occurs
What is the hog1 called in pombe for stress
Sty1
What is a target for sty1 in pombe
Atf1 mrna stabilisation
Atf1 is a tf important for antioxidant genes
What antioxidant enzyme which breaks down hydrogen peroxide binds sty1 in pombe to phosphorylate it during stress
Tpx1
