Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5-phosphatase, SHIP.

Stimulation of the B cell Ag receptor (BCR) has been reported to induce tyrosine phosphorylation of a 145-kDa protein and its association with the adapter protein Shc. We have identified this protein as the novel inositol polyphosphate 5-phosphatase (SHIP). Further analysis revealed that both maximal phosphorylation of SHIP and its association with Shc require co-clustering with the Fc receptor for IgG (Fc gamma RII) rather than stimulation of the BCR alone. Since co-clustering of the BCR and Fc gamma RII also down-regulates proliferation induced by Ag receptor stimulation, we hypothesize that tyrosine phosphorylation of SHIP and its association with Shc contribute to negative signaling through effects on inositol and phosphatidylinositol metabolism.