Abstract
Protein tyrosine phosphatase interacting protein 51 (PTPIP51), also known as regulator of microtubule dynamics protein 3, was identified as an in vitro and in vivo interaction partner of CGI-99 and Nuf-2. PTPIP51 mRNA is expressed in all stages of the cell cycle; it is highly expressed six hours post-nocodazole treatment and minimally expressed one hour post-nocodazole treatment. Recent investigations located PTPIP51 protein at the equatorial plate. This study reports the localization of the PTPIP51/CGI-99 and the PTPIP51/Nuf-2 complex at the equatorial region during mitosis. Moreover, Duolink proximity ligation assays revealed an association of PTPIP51 with the microtubular cytoskeleton and the spindle apparatus. High amounts of phosphorylated PTPIP51 associated with the spindle poles was seen by confocal microscopy. In parallel a strong interaction of PTPIP51 with the epidermal growth factor receptor phosphorylating PTPIP51 at the tyrosine 176 residue was seen. In the M/G1 transition a high level of interaction between PTPIP51 and PTP1B was registered, thus restoring the interaction of PTPIP51 and Raf-1, depleted in mitotic cells. Summarizing these new facts, we conclude that PTPIP51 is necessary for normal mitotic processes, impacting on chromosomal division and control of the MAPK pathway activity.
Highlights
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a multifunctional protein with implication in processes like proliferation, differentiation and apoptosis [1,2]
Raf-1 is tightly regulated by the raf kinase inhibitory protein (RKIP), which titrates the signal of the mitogen activated protein kinase (MAPK) pathway ensuring normal chromosomal segregation
Tyrosine phosphorylated PTPIP51 was observed in blasts of acute myeloid leukemia (AML)
Summary
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a multifunctional protein with implication in processes like proliferation, differentiation and apoptosis [1,2]. CGI-99 could inhibit the phosphorylation of hNinein mediated by glycogen synthase kinase 3 β, influencing the nucleation of the microtubules [15] These findings suggest PTPIP51 may play a pivotal role in mitotic processes, both in chromosomal segregation and cell signal titration. PTPIP51 interaction with the epidermal growth factor receptor and c-Src, the phosphatase PTP1B and Raf-1 was investigated by doulink proximity ligation assays. The acquired data suggest an involvement of PTPIP51 in correct chromosome segregation by the spindle apparatus, as well as for uncoupling Raf-1 from the MAPK pathway ensuring correct chromosomal segregation during cell cycle progression
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