SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 are dramatically increased at the protein level in neutrophils from patients with severecongenital neutropenia (Kostmann's syndrome)
N. Tidow et al., SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 are dramatically increased at the protein level in neutrophils from patients with severecongenital neutropenia (Kostmann's syndrome), EXP HEMATOL, 27(6), 1999, pp. 1038-1045
Severe congenital neutropenia (SCN) or Kostmann's syndrome is characterized
by a stop in differentiation of myeloid progenitor cells at the myelocytic
or promyelocytic stage. The pathophysiology of SCN is still unclear, We pr
eviously showed that the tyrosine kinase JAK2 is phosphorylated and activat
ed in neutrophils from patients with severe congential neutropenia, We inve
stigated the role of tyrosine phosphatases in this disease. Expression of t
he SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2 was analyzed
in myeloid cells from patients with SCN in comparison to healthy donors. W
e investigated tyrosine phosphatase expression in myeloid cells at the prot
ein level by Western blot analysis using polyclonal antisera against SHP-1
and SHP-2, Whereas SHP-1 and SHP-2 were hardly detectable in neutrophils fr
om healthy donors, neutrophils from patients with SCN revealed high amounts
of these two proteins in Western blot analyses. Reverse transcriptase-poly
merase chain reaction and Northern blot analyses demonstrated no dramatic d
ifferences of SHP-1 mRNA in neutrophils from congenital neutropenia patient
s as compared to healthy donors. SHP-2 mRNA was hardly detectable in the ne
utrophils from patients and in normal neutrophils. Increased expression of
SHP protein correlated with elevated activity of both SHP-1 and SHP-2 in ne
utrophils of patients with SCN, Taken together,these data indicate differen
tial regulation for SHP-1 and SHP-2 at the protein level in neutrophils fro
m SCN patients in comparison to healthy donors. We suggest that overexpress
ion of SHP-1 and SHP-2 protein in neutrophils and not in mononuclear cells
from patients with SCN might be related to the disease, e.g., by defective
dephosphorylation of proteins involved in intracellular signaling pathways.
(C) 1999 International Society for Experimental Hematology. Published by E
lsevier Science Inc.