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Biochem/physiol Actions

MKP3 (MAP (mitogen-activated protein) kinase phosphatase 3), or DUSP6 (dual specificity phosphatase 6), participates in one of the feedback loops regulating MAPK signal pathways in normal cell growth, where it dephosphorylates activated ERK (extracellular signal-regulated kinase) and inhibits growth-inducing signals. This protein localizes in the cytoplasm, and prevents ERK translocation to nucleus to act upon its effectors. In vitro studies in primary pancreatic cancer tissues show that this protein induces apoptosis and acts as a tumor suppressor gene. It acts as a negative feedback regulator of FGFR (fibroblast growth factor receptor) signaling, and mutations in this gene might be linked with unexplained FGFR-like syndrome cases. Expression levels of MKP3 gene in tumor samples might have potential as prognostic markers in non-small cell lung cancer (NSCLC), and the rs2279574 variant in MKP3 gene can help predict the chemoradiotherapy outcome in patients with inoperable NSCLC. In atypical endometrial hyperplasia (AEH), this gene can also help predict the effectiveness of progestin therapy.

The mitogen-activated protein kinase phosphatases (MKPs) are dual specificity phosphatases (DUSPs) that dephosphorylate phospho-Ser/Thr and phospho-Tyr residues. At least ten mammalian MPKs have been identified. MKPs have been studied for their important roles in MAPK related cancer cells and innate immune response. The MKP3, known as DUSP6 (dual specificity protein phosphatase 6), is a member of the protein tyrosine phosphatase superfamily. The MKP3 tightly regulates to ERK substrates by dephosphorylating both the phospho-Ser/Thr and phospho-Tyr residues. Its kinase interaction domain (KIM, residues 61-75) in addition to a conserved cytosolic domain (residues 161-177) and C-terminus domain (residues 348-381) plays an important role in ERK2 binding. Identification of specific activators or inhibitors of MKP3 and MPK1 may lead to the development of drug candidates against ERK pathway related diseases.

General description

MKP3 (MAP (mitogen-activated protein) kinase phosphatase 3), or DUSP6 (dual specificity phosphatase 6), gene is localized to human chromosome 12q22, and codes for extracellular signal-regulated kinase (ERK) specific dual-specificity phosphatase. MKP3 protein resides in the cytoplasm.

Physical form

Clear and colorless frozen liquid solution

Preparation Note

Use a manual defrost freezer and avoid repeated freeze-thaw cycles. While working, please keep sample on ice.