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MM9 - Dynamic Regulation of Protein (iii) (Phosphorylation (many functions…
MM9 - Dynamic Regulation of Protein (iii)
Phosphorylation
reversible
phosphate added to serine, threonine, tyrosine
ratio abundance = 100:10:1
tyrosine = least abundant, but when phosphorylated has greatest effect
tightly regulated
kinases phosphorylate
clinical targets...
chronic myelogenous leukemia
uncontrolled growth of myeloid cells in bone marrow, accumulate in blood
ABL gene of chromo 9 translocates to BCR gene of chromo 22 to form BCR-ABL (the Philadelphia chromo, abnormal, aggressive, uncontrollable)
BCR-ABL interacts with IL3 R+ drive myeloid cell proliferation
treatment = tyrosine kinase inhibitor (Gleevec, glivec, imitinib, Tasigna)
1st drug designed based on how disease works (rational drug design)
FDA-aproved in record time
phosphatases dephosphorylate
many functions
alters function
marks for degradation
alters location
promotes protein-protein interactions
FA modification
functions
membrane anchoring
protein would repel membrane otherwise
protein-protein interactions
reversible
types: farnesylation, myristoylation, palmitoylation, GPI-anchoring
Disregulation
CFTR mutation
can't be localised
loss of phosphorylation site
inactive protein
small GTPase mutation
cancers