title: PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14-3-3β and PTP1B in situ.
abstract: Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is an interaction partner of 14-3-3β, which correlates with the grade of malignancy in gliomas. In this study PTPIP51 and its interacting partners 14-3-3β, PTP1B, c-Src, Raf-1 as well as EGFR were investigated in human glioblastoma.   Twenty glioblastoma samples were analyzed on transcriptional and translational level by immunohistochemistry, in situ hybridization and RT-PCR. To compare PTPIP51 expression in gliomas of different malignancies, quantitative RT-PCR for grade II astrocytoma and GBM samples was employed. Additionally, we analyzed the correlation between PTPIP51 and 14-3-3β transcription, and checked for in situ interaction between PTPIP51 and 14-3-3β and PTP1B, respectively.   PTPIP51 and 14-3-3β mRNA showed a tumour grade dependent upregulation in gliomas. Glioblastoma cells displayed a strong immunoreaction of PTPIP51, which co-localized with 14-3-3β and PTP1B. The duolink proximity ligation assay corroborated a direct in situ interaction of PTPIP51 with both proteins, known to interact with PTPIP51 in vitro. The in vitro interacting partners Raf-1 and c-Src showed a partial co-localization. Besides, immune cells located in capillaries or infiltrating the tumour tissue and endothelial cells of pseudoglomerular vessels revealed a high PTPIP51 expression.   The upregulation of PTPIP51 and its connection with the EGFR/MAPK pathway by 14-3-3β via Raf-1 and by PTP1B via c-Src, argue for a functional role of PTPIP51 in the pathogenesis of human glioblastoma.
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany. meike.petri@anatomie.med.uni-giessen.de
authors.forename: M K
authors.initials: MK
authors.lastname: Petri
authors.forename: P
authors.initials: P
authors.lastname: Koch
authors.forename: A
authors.initials: A
authors.lastname: Stenzinger
authors.forename: K
authors.initials: K
authors.lastname: Kuchelmeister
authors.forename: U
authors.initials: U
authors.lastname: Nestler
authors.forename: A
authors.initials: A
authors.lastname: Paradowska
authors.forename: K
authors.initials: K
authors.lastname: Steger
authors.forename: A
authors.initials: A
authors.lastname: Brobeil
authors.forename: M
authors.initials: M
authors.lastname: Viard
authors.forename: M
authors.initials: M
authors.lastname: Wimmer
mesh_terms: D048948:14-3-3 Proteins / Q000032:analysis* / Q000235:genetics; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases; D005260:Female; D005858:Germany; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000235:genetics; D060787:Neoplasm Grading; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000032:analysis* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000032:analysis* / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D019061:src-Family Kinases / Q000032:analysis
chemical_list: D048948:14-3-3 Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C482982:YWHAB protein, human; D019061:src-Family Kinases; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C515449:RMDN3 protein, human