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.[1]References
- The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor. Taniguchi, Y., London, R., Schinkmann, K., Jiang, S., Avraham, H. Blood (1999) [Pubmed]
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