title: PTPIP51 is phosphorylated by Lyn and c-Src kinases lacking dephosphorylation by PTP1B in acute myeloid leukemia.
abstract: Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is known to be expressed in blood cells with restriction to the myeloid lineage. All myeloid progenitor cells are PTPIP51 positive except for the myeloblasts. To define the expression of PTPIP51 in acute myeloid leukemia (AML), we performed immunohistochemical experiments with peptide specific antibodies (C-terminus, N-terminus and aas 114-129) to PTPIP51 with samples of AML bone marrow trephine biopsy specimens. AML blasts reacted positive for PTPIP51 protein encompassing the C-terminal sequence. Healthy bone marrow displayed an exclusive staining for the N-terminal containing form of PTPIP51. Moreover, PTPIP51 protein was highly phosphorylated at its tyrosine 176 residue. Acquired confocal images of AML cells displayed an absence of PTP1B and revealed a co-localization of PTPIP51 and Lyn. Duolink proximity ligation assays (DPLA) corroborated an interaction for PTPIP51 with Lyn and c-Src. In AML blasts rarely an interaction of PTPIP51 with PTP1B and Raf-1 was seen. Furthermore, DPLA signals were also obtained for PTPIP51 and c-Kit in AML cells. Therefore, PTPIP51 was identified as a new signal molecule of the c-Kit signaling pathway. By the phosphorylation done by Lyn, c-Src and c-Kit, PTPIP51 is prevented to influence mitogen activated protein kinase pathway on Raf-1 level contributing to increased proliferation of AML cells.
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, Giessen 35392, Germany. Alexander.Brobeil@anatomie.med.uni-giessen.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Brobeil
authors.forename: Manuel
authors.initials: M
authors.lastname: Bobrich
authors.forename: Michaela
authors.initials: M
authors.lastname: Graf
authors.forename: Anke
authors.initials: A
authors.lastname: Kruchten
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Blau
authors.forename: Mathias
authors.initials: M
authors.lastname: Rummel
authors.forename: Sabine
authors.initials: S
authors.lastname: Oeschger
authors.forename: Klaus
authors.initials: K
authors.lastname: Steger
authors.forename: Monika
authors.initials: M
authors.lastname: Wimmer
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D000081247:CSK Tyrosine-Protein Kinase; D015342:DNA Probes; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D015342:DNA Probes; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D000081247:CSK Tyrosine-Protein Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C515449:RMDN3 protein, human