The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor.
We have recently isolated a cDNA encoding a novel human receptor-type tyrosine phosphatase, termed PTP-RO (for a protein tyrosine phosphatase receptor omicron), from 5-fluorouracil-treated murine bone marrow cells. PTP-RO is a human homologue of murine PTPlambda and is related to the homotypically adhering kappa and mu receptor-type tyrosine phosphatases. PTP-RO ... is expressed in human megakaryocytic cell lines, primary bone marrow megakaryocytes, and stem cells. PTP-RO mRNA and protein expression are upregulated upon phorbol 12-myristate 13-acetate (PMA) treatment of the megakaryocytic cell lines CMS, CMK, and Dami. To elucidate the function of PTP-RO in megakaryocytic cells and its potential involvement in the stem cell factor (SCF)/c-Kit receptor pathway, COS-7 and 293 cells were cotransfected with the cDNAs of both the c-Kit tyrosine kinase receptor and PTP-RO. PTP-RO was found to be associated with the c-Kit receptor in these transfected cells and the SCF/Kit ligand induced a rapid tyrosine phosphorylation of PTP-RO. Interestingly, these transfected cells demonstrated a decrease in their proliferative response to the SCF/Kit ligand. In addition, we assessed the association of PTP-RO with c-Kit in vivo. The results demonstrated that PTP-RO associates with c-Kit but not with the tyrosine kinase receptor FGF-R and that PTP-RO is tyrosine-phosphorylated after SCF stimulation of Mo7e and CMK cells. Antisense oligonucleotides directed against PTP-RO mRNA sequences significantly inhibited megakaryocyte progenitor proliferation. Therefore, these data show that the novel tyrosine kinase phosphatase PTP-RO is involved in megakaryocytopoiesis and that its function is mediated by the SCF/c-Kit pathway.
Mesh Terms:
Adolescent, Animals, COS Cells, Cadherins, Cell Differentiation, Cell Line, Cercopithecus aethiops, Cytoskeletal Proteins, Enzyme Induction, Female, Gene Expression Regulation, Developmental, Hematopoiesis, Humans, Leukemia, Myeloid, Acute, Megakaryocytes, Mice, Oligonucleotides, Antisense, Phosphorylation, Protein Processing, Post-Translational, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-kit, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Recombinant Fusion Proteins, Stem Cell Factor, Tetradecanoylphorbol Acetate, Trans-Activators, Transfection, Tumor Cells, Cultured, beta Catenin
Adolescent, Animals, COS Cells, Cadherins, Cell Differentiation, Cell Line, Cercopithecus aethiops, Cytoskeletal Proteins, Enzyme Induction, Female, Gene Expression Regulation, Developmental, Hematopoiesis, Humans, Leukemia, Myeloid, Acute, Megakaryocytes, Mice, Oligonucleotides, Antisense, Phosphorylation, Protein Processing, Post-Translational, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-kit, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Recombinant Fusion Proteins, Stem Cell Factor, Tetradecanoylphorbol Acetate, Trans-Activators, Transfection, Tumor Cells, Cultured, beta Catenin
Blood
Date: Jul. 15, 1999
PubMed ID: 10397721
View in: Pubmed Google Scholar
Download Curated Data For This Publication
5921
Switch View:
- Interactions 1