Association of src-kinase Lyn and non-src-kinase Syk with the granulocyte colony-stimulating factor receptor (G-CSFR) is not abrogated in neutrophils from severe congenital neutropenia patients with point mutations in the G-CSFR mRNA.

Severe congenital neutropenia (SCN) is characterized by a maturation arrest of myeloid progenitor cells at the stage of promyelocytes in bone marrow and low levels of mature neutrophils in peripheral blood. To date, little is known regarding the underlying pathomechanism of SCN. A defective response of neutrophil precursors to granulocyte colony-stimulating factor (G-CSF) is a suggested mechanism. In the last few years, we and others described point mutations in the cytoplasmic domain of the G-CSF receptor (G-CSFR) mRNA in a subgroup of SCN patients. In one allele of the G-CSFR gene, a C to T substitution resulted in a change from a glutamine codon to a stop codon. The expected G-CSFR proteins were truncated by 83 to 98 amino acids. In this study, we show that the Lyn and Syk kinases are associated with the G-CSFR in neutrophils from SCN patients with point mutations in the cytoplasmic domain of the G-CSFR mRNA. These findings provide additional proof of the expression of normal G-CSFRs in these patients, because the possible Syk binding motif is located between amino acid 727 and 747 in the G-CSFR.