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The human SHIP gene is differentially expressed in cell lineages of the
bone marrow and blood
SJ Geier, PA Algate, K Carlberg, D Flowers, C Friedman, B Trask and LR Rohrschneider
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092, USA.
The macrophage colony-stimulating factor receptor and several other
hematopoietic growth factor receptors induce the tyrosine phosphorylation
of a 145- to 150-kD protein in murine cells. We have previously cloned a
cDNA for the murine 150-kD protein, SHIP, and found that it encodes a
unique signaling intermediate that binds the SHC PTB domain through at
least one tyrosine phosphorylated (NPXY) site in the carboxyl-terminal
region. SHIP also contains several potential SH3 domain-binding sites, an
SH2 domain for binding other tyrosine phosphorylated proteins, and an
enzymatic activity that removes the phosphate from the 5 position of
phosphatidylinositol 3,4,5-phosphate or from inositol 1,3,4,5-phosphate.
SHIP has a negative effect on cell growth and therefore loss or
modification may have profound effects on hematopoietic cell development.
In this study, we have cloned a cDNA for human SHIP and examined mRNA and
protein expression of SHIP and related species in bone marrow and blood
cells. Flow cytometry indicates that at least 74% of immature CD34+ cells
express SHIP cross- reacting protein species, whereas within the more
mature population of CD33+ cells, only 10% of cells have similar
expression. The majority of T cells react positively with the anti-SHIP
antibodies, but significantly fewer B cells are positive. Immunoblotting
detects up to seven different cross-reacting SHIP species, with peripheral
blood mononuclear cells exhibiting primarily a 100-kD protein and a CD34+
acute myeloblastic leukemia expressing mainly 130-kD and 145-kD forms of
SHIP. Overall, these results indicate that there is an enormous diversity
in the size of SHIP or SHIP-related mRNA and protein species. Furthermore,
the expression of these protein species changes according to both the
developmental stage and differentiated lineage of the mature blood cell.
Volume 89,
Issue 6,
pp. 1876-1885,
03/15/1997
Copyright © 1997 by The American Society of Hematology

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