Gab Adapter Proteins as Therapeutic Targets for Hematologic Disease
Potential of stapled peptides in therapeutic intervention. Step 1 illustrates how Erk phosphorylates Gab2 on a consensus phosphorylation site at serine 623, a residue located between tyrosine 614 and tyrosine 643, which are responsible for Gab2/Src homology 2 domain-containing tyrosine phosphatase- (SHP-) 2 interaction. As is reported in the text, this is part of a negative feedback loop. Hypothetically a stapled peptide (SP), a biosynthetic molecule binding to a directed region on Gab2, could be introduced in Step 2 to block the negative regulation by Erk to keep SHP-2 active and STAT5 inactive. Alternatively, it may be necessary to block SHP-2 binding to Gab2 depending on the disease entity. This figure elaborates how targeted therapy might provide new direction into understanding the interactions between adapters, like Gabs, and their partners, and which could ultimately be applied as leukemia therapy.
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