当前位置： SCI文献检索 > BLOOD期刊下所有文献 > 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.

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.

Abstract：

: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.

journal_name

Blood

journal_title

Blood

authors

Mirza AM,Correa PN,Axelrad AA

subject

Has Abstract

pub_date

1995-08-01 00:00:00

pages

877-82

issue

eissn

0006-4971

issn

1528-0020

journal_volume

pub_type

杂志文章

在线工具

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.