Disease relevance of Dusp4

• The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase [1].
• MKP-2 was undetectable in normal liver but strongly expressed in hepatomas [2].

High impact information on Dusp4

• RA up-regulated the expression level of MAP kinase phosphatase-1 (MKP-1) and MKP-2, and the time course was correlated with the inhibitory effect of RA on activation of MAP kinases [3].
• Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) and MKP-2 are two members of a recently described family of dual specificity phosphatases that are capable of dephosphorylating p42/p44MAPK [4].
• To analyze the contribution of the MAP kinase cascade to MKP-1 and MKP-2 induction, we examined CCL39 cells transformed with either v-ras or a constitutively active direct upstream activator of MAP kinase, mitogen-activated protein kinase kinase-1 (MKK-1; MKK-1(SD/SD) mutant) [4].
• Overexpression of MKP-1 or MKP-2 inhibits MAP kinase-dependent intracellular signaling events and fibroblast proliferation [4].
• We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells [5].

Biological context of Dusp4

• MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions [5].
• The MKP-2 mRNA level was increased with expression of malignant phenotypes in hepatomas [2].

Anatomical context of Dusp4

• In contrast, MKP2 is induced mainly in the dentate gyrus and MKP3 is preferentially increased in the CA1 and CA3 cell layers [6].
• MAP kinase phosphatase-2 (MKP-2) is a member of a family of dual specificity phosphatases (DSPs) that function in both the cytosol and nucleus to inactivate the MAP kinases [7].

Associations of Dusp4 with chemical compounds

• MKP-2 showed significant homology with MKP-1 (58.8% at the amino acid level) and, like MKP-1, displayed vanadate-sensitive phosphatase activity against MAP kinase in vitro [5].
• Moxonidine and NGF both increased levels of MKP-2 by three-fold [1].
• Moxonidine-induced induction of MKP-2 was time- and dose-dependent and could be blocked by the I(1)-antagonist efaroxan or by D609, an inhibitor of phosphatidylcholine-selective phospholipase C known to block downstream signaling events coupled to I(1)-receptors [1].
• Induction of MKP-2 by GnRH was dependent on elevation in intracellular Ca(2+) [8].
• Activation of mitogen-activated protein kinase phosphatase 2 by gonadotropin-releasing hormone [8].

Other interactions of Dusp4

• Protein phosphotase-1 and mitogen-activated protein kinase phosphatase-2, which dephosphorylates phospho-ERK, were also measured, but they were not altered by TSD [9].

References