Distribution of the Src-homology-2-domain-containing inositol 5-phosphatase SHIP-2 in both non-haemopoietic and haemopoietic cells and possible involvement of SHIP-2 in negative signalling of B-cells

The termination of activation signals is a critical step in the control of the immune response; perturbation of inhibitory feedback pathways results i n profound immune defects culminating in autoimmunity and overwhelming infl ammation. Fc gamma RIIB receptor is a well described inhibitory receptor. T he ligation of B-cell receptor (BCR) and Fc gamma RIIB leads to the inhibit ion of B-cell activation. Numerous studies have demonstrated that the SH2-d omain-containing inositol 5-phosphatase SHIP (referred hereto as SHIP-1) is essential in this process. The cDNA encoding a second SH2-domain-containin g inositol 5-phosphatase, SHIP-2, has been cloned [Pesesse, Deleu, De Smedt , Drayer and Erneux (1997) Biochem. Biophys. Res. Commun. 239, 697-700]. He re we report the distribution of SHIP-2 in mouse tissues. a Western blot an alysis of mouse tissues reveals that SHIP-2 is expressed in both haemopoiet ic and non-haemopoietic cells. In addition to T-cell and B-cell lines, sple en, thymus and lung are shown to coexpress SHIP-1 and SHIP-2. Moreover, SHI P-2 is detected in fibroblasts, heart and different brain areas. SHIP-2 sho ws a maximal tyrosine phosphorylation and association to Shc after ligation of BCR to Fc gamma RIIB but not after stimulation of BCR alone. Our result s therefore suggest a possible role for SHIP-2 in the negative regulation o f immunocompetent cells.