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PTPIP51—A New RelA-tionship with the NFκB Signaling Pathway.

Brobeil A, Kämmerer F, Tag C, Steger K, Gattenlöhner S, Wimmer M - Biomolecules (2015)

Bottom Line: This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα.Here, PTPIP51 and Raf-1 interactions were slightly repressed.The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University, Gießen 35392, Germany. alexander.brobeil@patho.med.uni-giessen.de.

ABSTRACT
The present study shows a new connection of protein tyrosine phosphatase interacting protein 51 (PTPIP51) to the nuclear factor κB (NFκB) signalling pathway. PTPIP51 mRNA and protein expression is regulated by RelA. If bound to the PTPIP51 promoter, RelA repress the mRNA and protein expression of PTPIP51. The parallel treatment with pyrrolidine dithiocarbamate (PDTC) reversed the suppression of PTPIP51 protein expression induced by TNFα. Using the intensity correlation analysis PTPIP51 verified a co-localization with RelA, which is also regulated by TNFα administration. Moreover, the direct interaction of PTPIP51 and RelA was established using the DuoLink proximity ligation assay. IκBα, the known inhibitor of RelA, also interacted with PTPIP51. This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα. The PTPIP51/RelA/IκBα complex is modulated by TNFα. Interestingly, the impact on the mitogen activated protein kinase pathway was negligible except in highest TNFα concentration. Here, PTPIP51 and Raf-1 interactions were slightly repressed. The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact.

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Related in: MedlinePlus

Quantitative analysis of PTPIP51 and PKA, PTPIP51 and PTP1B interactions evaluated by Duolink Image Tool software. (A) PTPIP51 and PKA interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. *** (p < 0.001); (B) PTPIP51 and PTP1B interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. The resulting data were analyzed by GraphPad Prism 6 software, significance of results tested by Dunnett’s multiple comparisons test.
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biomolecules-05-00485-f009: Quantitative analysis of PTPIP51 and PKA, PTPIP51 and PTP1B interactions evaluated by Duolink Image Tool software. (A) PTPIP51 and PKA interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. *** (p < 0.001); (B) PTPIP51 and PTP1B interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. The resulting data were analyzed by GraphPad Prism 6 software, significance of results tested by Dunnett’s multiple comparisons test.

Mentions: The interactions of PTPIP51 are regulated by its serine phosphorylation status regulated by Protein kinase A. Thus, we investigated the interaction of PTPIP51 with PKA in HaCaT cells submitted to TNFα in increasing concentrations. 50 ng and 100 ng TNFα had no significant influence on PTPIP51/PKA interaction. Using 200 ng TNFα significantly reduced the interaction, whereas 400 ng led to near normal values and 500 ng restored the low interaction rate seen with 200 ng (Figure 9A).


PTPIP51—A New RelA-tionship with the NFκB Signaling Pathway.

Brobeil A, Kämmerer F, Tag C, Steger K, Gattenlöhner S, Wimmer M - Biomolecules (2015)

Quantitative analysis of PTPIP51 and PKA, PTPIP51 and PTP1B interactions evaluated by Duolink Image Tool software. (A) PTPIP51 and PKA interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. *** (p < 0.001); (B) PTPIP51 and PTP1B interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. The resulting data were analyzed by GraphPad Prism 6 software, significance of results tested by Dunnett’s multiple comparisons test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496682&req=5

biomolecules-05-00485-f009: Quantitative analysis of PTPIP51 and PKA, PTPIP51 and PTP1B interactions evaluated by Duolink Image Tool software. (A) PTPIP51 and PKA interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. *** (p < 0.001); (B) PTPIP51 and PTP1B interactions. Untreated controls, 50 ng/mL TNFα treated cells, 100 ng/mL TNFα treated cells, 200 ng/mL TNFα treated cells, 400 ng/mL TNFα treated cells, 500 ng/mL TNFα treated cells. The resulting data were analyzed by GraphPad Prism 6 software, significance of results tested by Dunnett’s multiple comparisons test.
Mentions: The interactions of PTPIP51 are regulated by its serine phosphorylation status regulated by Protein kinase A. Thus, we investigated the interaction of PTPIP51 with PKA in HaCaT cells submitted to TNFα in increasing concentrations. 50 ng and 100 ng TNFα had no significant influence on PTPIP51/PKA interaction. Using 200 ng TNFα significantly reduced the interaction, whereas 400 ng led to near normal values and 500 ng restored the low interaction rate seen with 200 ng (Figure 9A).

Bottom Line: This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα.Here, PTPIP51 and Raf-1 interactions were slightly repressed.The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact.

View Article: PubMed Central - PubMed

Affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University, Gießen 35392, Germany. alexander.brobeil@patho.med.uni-giessen.de.

ABSTRACT
The present study shows a new connection of protein tyrosine phosphatase interacting protein 51 (PTPIP51) to the nuclear factor κB (NFκB) signalling pathway. PTPIP51 mRNA and protein expression is regulated by RelA. If bound to the PTPIP51 promoter, RelA repress the mRNA and protein expression of PTPIP51. The parallel treatment with pyrrolidine dithiocarbamate (PDTC) reversed the suppression of PTPIP51 protein expression induced by TNFα. Using the intensity correlation analysis PTPIP51 verified a co-localization with RelA, which is also regulated by TNFα administration. Moreover, the direct interaction of PTPIP51 and RelA was established using the DuoLink proximity ligation assay. IκBα, the known inhibitor of RelA, also interacted with PTPIP51. This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα. The PTPIP51/RelA/IκBα complex is modulated by TNFα. Interestingly, the impact on the mitogen activated protein kinase pathway was negligible except in highest TNFα concentration. Here, PTPIP51 and Raf-1 interactions were slightly repressed. The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact.

Show MeSH
Related in: MedlinePlus