Association of Tyrosine Phosphatases SHP-1 and SHP-2, Inositol 5-Phosphatase SHIP with gp49B1, and Chromosomal Assignment of the Gene*

We have analyzed the molecules participating in the inhibitory function of gp49B1, a murine type I transmembrane glycoprotein expressed on mast cells and natural killer cells, as well as the chromosomal location of its gene. As assessed by SDS-polyacrylamide gel electrophoresis and immunoblot analysis, tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching each of the two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences found in the cytoplasmic portion of gp49B1 associated with the ∼65-kDa tyrosine phosphatase SHP-1 and ∼70-kDa SHP-2 derived from RBL-2H3 cells. In addition, the phosphotyrosyl peptide matching the second ITIM-like sequence also bound the ∼145-kDa inositol polyphosphate 5-phosphatase SHIP. Thus, it has been strongly suggested that the inhibitory nature of gp49B involves the recruitment of SHP-1, SHP-2, and SHIP for the delivery of inhibitory signal to the cell interior upon phosphorylation of tyrosine residues in their ITIMs. The gp49B gene has been found to be in the juxtaposition of its cognate gene, gp49A. The gene pair was shown to locate in the B4 band of mouse chromosome 10. In this region, no conserved linkage homology to human chromosome 19, where the genes for killer cell inhibitory receptors are found, has been identified.