Increased G-CSF responsiveness of bone marrow cells from hematopoietic cell phosphatase deficient viable motheaten mice.
The mouse mutation viable motheaten (me(v)) results in defects in the expression and catalytic activity of the cytoplasmic protein tyrosine phosphatase known as hematopoietic cell phosphatase (HCP). This reduction in HCP activity leads to the aberrant regulation of several myeloid and lymphoid cell lineages, including substantial increases in numbers of granulocytes. The differentiation, proliferation, and survival of cells in this lineage are normally supported by granulocyte-colony stimulating factor (G-CSF). In this study we have determined the consequences of the loss of HCP activity in me(v)/me(v) mice on the response of bone marrow cells to G-CSF. Bone marrow from these mice exhibited substantial increases in clonogenic and proliferative responses to G-CSF. These enhanced activities of G-CSF correlated with an increase in the level of immature granulocytic, G-CSF receptor positive cells in the bone marrow. These results suggested the possibility that HCP may regulate the G-CSF receptor by a direct interaction. However, under conditions where the previously described interaction between the erythropoietin receptor and HCP was readily observed, HCP did not detectably associate with the G-CSF receptor.
Tapley
P
P
Ligand Pharmaceuticals Inc., San Diego, CA 92121, USA.
Shevde
N K
NK
Schweitzer
P A
PA
Gallina
M
M
Christianson
S W
SW
Lin
I L
IL
Stein
R B
RB
Shultz
L D
LD
Rosen
J
J
Lamb
P
P
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D007964:Leukocytosis / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000473:pathology; D011499:Protein Processing, Post-Translational; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse