Next Article in Journal
Suppression of mRNA Nanoparticle Transfection in Human Fibroblasts by Selected Interferon Inhibiting Small Molecule Compounds
Previous Article in Journal
The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii
Article Menu

Export Article

Open AccessArticle
Biomolecules 2017, 7(3), 55;

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35392 Giessen, Germany
Institute of Pathology, Justus-Liebig-University, 35392 Giessen, Germany
Author to whom correspondence should be addressed.
Academic Editor: Jürg Bähler
Received: 18 April 2017 / Revised: 14 July 2017 / Accepted: 19 July 2017 / Published: 21 July 2017
Full-Text   |   PDF [3857 KB, uploaded 25 July 2017]   |  


Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity. Small interfering ribonucleic acid (siRNA) experiments show that the modification in PTPIP51 binding capacity is induced by LDC-3. Application of LDC-3 annuls the known regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly alters the assembly of the PTPIP51 associated protein complexes. The treatment of human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein–protein interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3 stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex composed of Raf-1 and the scaffold protein 14-3-3, independent of the phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the unique opportunity to directly modulate PTPIP51 in malignant cells, thus targeting potential dysregulated signal transduction pathways such as the MAPK cascade. The provided data give critical insights in the therapeutic potential of PTPIP51 protein interactions and thus are basic for possible targeted therapy regimens. View Full-Text
Keywords: PTPIP51; LDC-3; protein–protein interaction; protein complex; scaffold protein PTPIP51; LDC-3; protein–protein interaction; protein complex; scaffold protein

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Brobeil, A.; Chehab, R.; Dietel, E.; Gattenlöhner, S.; Wimmer, M. Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling. Biomolecules 2017, 7, 55.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top