PP2 is a substance that has frequently been used in cancer research as a "selective" inhibitor for Src-family kinases. It strongly inhibits the kinases Lck (IC<sub>50</sub>=4 nM), Fyn (5 nM) and Hck (5 nM), shows weaker inhibition of epidermal growth factor receptor (480 nM) and practically no inhibition of ZAP-70 (100 üM) and JAK2 (50 üM). Despite its extensive use as a Src-selective inhibitor, recent research has shown that PP2 is non-selective and inhibits many other kinases with similar affinities.
PP2A is a heterotrimeric enzyme composed of three types of subunits:
The diversity of the B subunit family allows PP2A to form multiple holoenzymes with distinct functions, enabling it to regulate numerous cellular processes with high specificity.
The central mechanisms in the regulation of most cellular processes include protein phosphorylation and dephosphorylation. PP2 enzymes specifically target proteins that are phosphorylated on serine and threonine residues. The dephosphorylation reaction typically requires water molecules and is catalyzed by a conserved active site in the PP2 enzyme.
The primary function of PP2 is to reverse the actions of kinases, which add phosphate groups to proteins. By removing phosphate groups, PP2 modulates the activity, location, and interaction of the target proteins, thereby controlling various aspects of cell behavior.
Due to its role in controlling phosphorylation status, PP2A is implicated in various physiological and pathological conditions: