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The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor
journal contribution
posted on 2000-07-01, 00:00 authored by Alister WardAlister Ward, S P M A Oomen, L Smith, J Gits, D van Leeuwen, A A Soede-Bobok, C A J Erpelinck-Verschueren, T Yi, I P TouwThe SH2 domain-containing protein tyrosine phosphatase SHP-1 is expressed widely in the hematopoietic system. SHP-1 has been shown to negatively control signal transduction from many cytokine receptors by direct docking to either the receptor itself, or to members of the Jak family of tyrosine kinases which are themselves part of the receptor complex. Motheaten and viable motheaten mice, which are deficient in SHP-1, have increased myelopoiesis and show an accumulation of morphologically and phenotypically immature granulocytes, suggesting a role for SHP-1 in granulocytic differentiation. Here, we report that SHP-1 protein levels are up-regulated during the granulocyte colony-stimulating factor (G-CSF)-mediated granulocytic differentiation of myeloid 32D cells. Enforced expression of SHP-1 in these cells leads to decreased proliferation and enhanced differentiation, while introduction of a catalytically inactive mutant produces increased proliferation and results in a delay of differentiation. In vitro binding revealed that the SH2 domains of SHP-1 are unable to associate directly with tyrosine-phosphorylated G-CSF receptor (G-CSF-R). Furthermore, over-expression of SHP-1 in Ba/F3 cells expressing a G-CSF-R mutant lacking all cytoplasmic tyrosines also inhibited proliferation. Together, these data suggest that SHP-1 directly modulates G-CSF-mediated responses in hematopoietic cells via a mechanism that does not require docking to the activated G-CSF-R.
History
Journal
LeukemiaVolume
14Issue
7Pagination
1284 - 1291Publisher
Nature Publishing GroupLocation
London, Eng.ISSN
0887-6924Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2000, Macmillan Publishers LtdUsage metrics
Categories
Keywords
AnimalsCell DifferentiationCell DivisionGene Expression RegulationGene Expression Regulation, LeukemicGranulocyte Colony-Stimulating FactorHematopoietic Stem CellsHumansInterleukin-3Intracellular Signaling Peptides and ProteinsMiceNeoplasm ProteinsPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, Granulocyte Colony-Stimulating FactorRecombinant Fusion ProteinsSH2 Domain-Containing Protein Tyrosine PhosphatasesSignal TransductionTransfectionTumor Cells, Culturedsrc Homology DomainsScience & TechnologyLife Sciences & BiomedicineOncologyHematologycytokine receptorsgranulopoiesisG-CSFHEMATOPOIETIC-CELL PHOSPHATASESEVERE CONGENITAL NEUTROPENIAMOTH-EATEN MICERAPID ACTIVATIONPHOSPHOTYROSINE PHOSPHATASEEXPRESSION CLONINGMYELOID-LEUKEMIAINTERFERON-GAMMAVIABLE MOTHEATENBINDING PROTEIN