Mitogen-activated protein (MAP) kinases are a large class of proteins involved in signal transduction pathways, which are activated by a range of stimuli and mediate a number of physiological and pathological changes in the cell. Dual specificity phosphatases (DUSPs) are a subclass of the protein tyrosine phosphatase (PTP) gene superfamily, which are selective for dephosphorylating critical phosphothreonine and phosphotyrosine residues within MAP kinases. DUSP gene expression is induced by a host of growth factors and/or cellular stresses, thereby negatively regulating MAP kinase superfamily members including MAPK/ERK, SAPK/JNK and p38. DUSP26, also designated LDP4, MKP8, NATA1 and SKRP3, is ubiquitously expressed in brain except in the hippocampus. DUSP26 dephosphorylates p38 thereby inhibiting p38-mediated apoptosis in anaplastic thyroid cancer cells. Downregulation of DUSP26 may also contribute to malignant phenotypes of glioma.
