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Expression and functionality of the trkA proto-oncogene product/NGF
receptor in undifferentiated hematopoietic cells
S Chevalier, V Praloran, C Smith, D MacGrogan, NY Ip, GD Yancopoulos, P Brachet, A Pouplard and H Gascan
Neurobiologie et immunopathologie des maladies du systeme nerveux, INSERM
U298, CHRU Angers, France.
The expression of the low-affinity NGF receptor (p75) and the trkA
proto-oncogene product was analyzed in a series of human hematopoietic cell
lines at protein and RNA levels. We did not detect any form of NGF receptor
in cell lines displaying a myelomonocytic phenotype (HL60 and U937). In
contrast, cells displaying a more immature erythroleukemic phenotype (TF1
and K562) expressed TrkA in the absence of detectable p75. Scatchard
analysis showed a single high-affinity site for NGF (kd = 10(-10) mol/L),
with a copy number ranging from 300 to 3,000 sites per cell depending on
the studied cell line. In addition, NGF induced autophosphorylation of TrkA
and could substitute for granulocyte- monocyte colony-stimulating factor to
trigger the proliferation of the TF1 cell line, with a half-maximal signal
observed at 50 pmol/L, indicating that p75 is not required for DNA
synthesis in this cell line. The physiologic relevance of NGF in early
hematopoiesis was confirmed by showing that 12% to 15% of progenitor blood
cells from mice treated with 5-fluorouracil expressed TrkA and that these
cells could be induced to proliferate and differentiate in response to NGF
in association with macrophage colony-stimulating factor. Our study
demonstrates for the first time that trkA proto-oncogene expression and
activation is not restricted to the nervous system, but is also an
important element in early hematopoiesis.
Volume 83,
Issue 6,
pp. 1479-1485,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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