Interaction of PTPIP51 with Tubulin, CGI-99 and Nuf2 During Cell Cycle Progression

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.

The protein tyrosine phosphatase interacting protein 51 (PTPIP51) is required for the differentiation of photoreceptors

“…Regarding the photoreceptor inner segments, the co-localization of PTPIP51 with the ATP-synthase, a mitochondrial marker, suggests the association of PTPIP51 with this organelle, as previously described in other cell types (Lv et al, 2006;De Vos et al, 2012;Stoica et al, 2014). The variability of the subcellular localization in the rat retina is in agreement with previous studies, which reported different localization for PTPIP51 according to the cell type, but also resulting from the phosphorylation status of PTPIP51 and from the type of the interacting proteins involved (Stenzinger et al, 2009b;Brobeil et al, 2010Brobeil et al, , 2012Bobrich et al, 2013). Furthermore, different isoforms of variable molecular weight have been observed in many tissues, including mouse brain and retina (Stenzinger et al, 2005(Stenzinger et al, , 2009aMaerker et al, 2008;Koch et al, 2009;Brobeil et al, 2010).…”

“…The PTPIP51 protein also known as regulator of microtubule dynamics protein 3 (RMD-3) belongs to a family of microtubule-associated proteins and its interaction with microtubular cytoskeleton has been recently demonstrated by duolink proximity ligation assay (Brobeil et al, 2012). A potential role of PTPIP51 in cell morphology and motility has been postulated in different cell lines via its interaction with the 14-3-3 adaptorscaffold protein (Yu et al, 2008).…”

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

“…Interestingly, the interaction with the relevant tyrosine phosphatase PTP1B was unaffected by the administration of TNFα. Therefore, we conclude that PTP1B exerts its regulatory function on PTPIP51/Raf-1 binding levels when the main tyrosine receptor kinases are activated, such as the epidermal growth factor rector (EGFR) [ 2 , 4 ]. PKA is assumed to titrate the activation of PTPIP51/RelA mediated MAPK pathway activation.…”

“…Options were set for all confocal acquired images as follows: 8—numbers of iteration; and 2.0 pixels—LP filter diameter. Point spread function was calculated for each channel separately by the ImageJ plug-in created by Bob Dougherty [ 4 ].…”

“…Here, PTPIP51 is under control of distinct kinases and phosphatases modulating its binding capability to Raf-1 and thereby titrating the MAPK signal [ 1 , 2 , 3 ]. Moreover, the protein interactions of PTPIP51 are associated with cell cycle progression and PTPIP51 plays a pivotal role during chromosome segregation [ 4 ].…”