High impact information on PPM1B

• PP2Cbeta association with the IKK complex led to the dephosphorylation of IKKbeta and decreased its kinase activity [1].
• Collectively, these results indicate that PP2Cbeta negatively regulates the TAK1 signaling pathway by direct dephosphorylation of TAK1 [2].
• In contrast, dephosphorylation proceeded more slowly with CDK2(Ser-160) than with wild-type CDK2, either in HeLa cell extract or by purified PP2Cbeta [3].
• Overexpression of PP2Cbeta under CMV-promoter in 293 cells led to cell-growth arrest or cell death [4].
• The results provide novel insights in endothelial apoptosis and suggest that PP2Cbeta participates in the development and progress of atherosclerosis [5].

Biological context of PPM1B

• The cloning expression and tissue distribution of human PP2Cbeta [6].
• We have cloned a novel PP2Cbeta isoform from a human liver cDNA library which codes for a protein homologous to other mammalian PP2Cbetas at the N-terminus but with an extended C-terminus that is unique amongst the PP2Cs [6].
• Lipophilic compounds that stimulated PP2Cbeta activity in vitro were found to induce cell death of HUVECs [5].
• However, basal as well as serum-activated phosphorylation of MKK1alpha, an upstream protein kinase of ERKs, was not affected by PP2Cbeta or PP2Cbeta-1 [7].
• Transient transfections of COS or BHK cells with pCMV2 derived vectors containing these constructs showed that the expressed hybrid protein with the lowest activity (N-terminal tagged < untagged < C-terminal tagged PP2C beta 1) was expressed to the highest level and vice versa [8].

Anatomical context of PPM1B

• Northern blot analysis of PP2Cbeta along with that of PP2Calpha shows that human PP2Cs are widely expressed and are most abundant in heart and skeletal muscle [6].
• Here, we present evidence for the presence of protein phosphatase type 2Cbeta (PP2Cbeta) in human umbilical vein endothelial cells (HUVECs) and report on colocalization of PP2Cbeta and Bad in the cytosol of endothelial cells [5].
• The nuclei remained stained even after selective perforation of the plasma membrane with digitonin and washing out the cytosolic PP2C beta 1 [8].

Associations of PPM1B with chemical compounds

• Analytical methods revealed that both effects - stimulation of PP2Cbeta and apoptosis - were caused by free fatty acids liberated from VLDL, LDL and HDL with oleic acid and linoleic acid as major constituents [5].
• Using RNA interference to reduce the amount of PP2Calpha and PP2Cbeta results in cells significantly less susceptible to the apoptotic effect of oleic acid [9].

Other interactions of PPM1B

• The binding of PP2Cbeta to IKKbeta was decreased at early times post-tumor necrosis factor-alpha treatment and was restored at later times following treatment with this cytokine [1].
• Lipoproteins treated with the lipoprotein lipase, however, stimulated the activity of PP2Cbeta at least 10-fold concomitantly triggering cell death [5].
• We have recently elucidated the structure of an isoform of the Mg(2+)-dependent protein phosphatase 2C (PP2C beta 1) from rat liver (Wenk, J., H.-I. Trompeter, K.-G. Pettrich, P. T. W. Cohen, D. G. Campbell, G. Mieskes, FEBS Lett. 297, 135-138 (1992)) [8].

Analytical, diagnostic and therapeutic context of PPM1B

• In immunofluorescence studies with antibodies specific for the PP2C beta isoform, all overexpressed proteins showed the expected cytoplasmic as well as a significant nuclear localization [8].

References