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Increased basal and induced tyrosine phosphorylation of the insulin- like
growth factor I receptor beta subunit in circulating mononuclear cells of
patients with polycythemia vera
AM Mirza, PN Correa and AA Axelrad
Department of Anatomy and Cell Biology, University of Toronto, Ontario,
Canada.
We have previously shown that circulating progenitor cells in patients with
polycythemia vera (PV) are hypersensitive to insulin-like growth factor I
(IGF-I) with respect to erythroid burst formation in serum- free medium,
and that this effect occurs through the IGF-I receptor. To investigate the
molecular basis of this IGF-I hypersensitivity phenomenon, we examined
tyrosine phosphorylation of the IGF-I receptor beta subunit in peripheral
blood mononuclear cells (PBMNC) from eight PV patients and six normals.
Cells were exposed to IGF-I at concentrations of 10(-8) and 10(-10) mol/L
for 0, 1, 3, and 10 minutes, and then lysed. The IGF-I receptor beta
subunit was immunoprecipitated, and the protein was resolved by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotted with
antiphosphotyrosine antibody (4G10). We found that, in the absence of
exogenous IGF-I, there was a basal level of tyrosine phosphorylation of the
IGF-I receptor beta subunit, and it was substantially greater in PV than in
normal. At 10(-10) mol/L IGF-I in normals, no evidence of increased
tyrosine phosphorylation was detected; however in PV, a pronounced increase
in tyrosine phosphorylation was observed at both 10(-10) and 10(-8) mol/L
IGF-I, and it occurred earlier and attained a higher level than in normal.
In contrast, in PBMNC from three patients with erythrocytosis, no
significant increase above normal was seen in either basal or induced
tyrosine phosphorylation of the IGF-I receptor beta subunit. Thus, our
findings show two distinctive features of the PV phenotype in PBMNC: (1) an
increased basal tyrosine phosphorylation of the IGF-I receptor beta
subunit, and (2) a hypersensitive and hyperresponsive receptor with respect
to tyrosine phosphorylation. These features may influence the ability of
the receptor to transmit a proliferative signal; thus, they may play a role
in the pathogenesis of PV.
Volume 86,
Issue 3,
pp. 877-882,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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