Serine/threonine protein phosphatases in apoptosis.
The importance of phosphorylation and dephosphorylation in intracellular signaling pathways has long been recognized, although attention has focused mainly on kinases. Recent studies have highlighted the importance of serine/threonine protein phosphatases in many processes including apoptosis. The phosphorylation state of antiapoptotic (Bcl-2, Bcl-X(L)) and proapoptotic (BAD, Bid, Bik) Bcl-2 proteins regulates their cellular activity and, therefore, cell survival and cell death. For example, dephosphorylation of BAD by the protein phosphatases PP1, PP2A and PP2B allows BAD to interact with Bcl-X(L) and initiate cell death. Caspases are also important in cell death and phosphorylation/dephosphorylation of caspases themselves, their targets and their regulators modulates apoptotic pathways. The activity of serine/threonine protein phosphatases needs further study, but it is clear that these enzymes are potential targets for novel therapeutics with applications in many diseases, including cancer, inflammatory diseases and neurodegeneration.
Westfälische Wilhelms-Universität, Institut für Pharmazeutische und Medizinische Chemie, Hittorfstrasse 58-62, D-48149, Münster, Germany. klumpp@uni-muenster.de
Susanne
S
Klumpp
Josef
J
Krieglstein
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases