The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood.
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.
Geier
S J
SJ
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092, USA.
Algate
P A
PA
Carlberg
K
K
Flowers
D
D
Friedman
C
C
Trask
B
B
Rohrschneider
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000302:isolation & purification; D014407:Tumor Cells, Cultured; D018909:src Homology Domains / Q000235:genetics*
D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases