Mitogen-Activated Protein Kinase Phosphatase 1 (MKP-1)

MAP kinase phosphatase 1 (MKP-1), also known as dual-specificity phosphatase 1 (DUSP1), is a nuclear-localized, inducible enzyme that plays a critical role in the negative regulation of mitogen-activated protein kinase (MAPK) signaling pathways. MKP-1 is the founding member of the MAPK phosphatases family and acts as an immediate-early gene product, rapidly induced by various cellular stresses and stimuli such as oxidative stress, growth factors, cytokines, fatty acids, glucocorticoids, hypoxia, and UV radiation. MKP‑1 functions as a dual-specificity phosphatase that dephosphorylates both threonine and tyrosine residues on activated MAPKs. This action inactivates key kinases including ERK (extracellular signal-regulated kinases), JNKs (c-Jun N-terminal kinases), and p38 MAPKs—though substrate preference can vary by cell type or context. By doing so, it provides negative feedback control over MAPK signaling cascades and regulates processes such as gene expression, cell proliferation/differentiation/survival/death responses to stressors. Given its central role in controlling inflammation/metabolism via modulation of MAPK activity, dysregulation contributes to chronic inflammatory diseases/metabolic syndromes, making it a potential therapeutic target for modulating immune responses or treating metabolic disorders.

Other names

DUSP1

Dephosphorylation of threonine and tyrosine residues on MAP kinases (ERKs, JNKs, p38)