CUTTING EDGE - ROLE OF THE INOSITOL PHOSPHATASE SHIP IN B-CELL RECEPTOR-INDUCED CA2+ OSCILLATORY RESPONSE

Src homology-2 domain-containing inositol polyphosphate 5-'phosphatase (SHIP) is a recently identified protein that has been implicated as a n important signaling molecule. Although SHIP has been shown to partic ipate in the Fc gamma RIIB-mediated inhibitory signal, the functional role of SHIP in activation responses by immunoreceptor tyrosine-based activation motif-bearing receptors such as B cell receptor (BCR) remai ns unclear. Indeed, it has been proposed that SHIP serves as a linking molecule for the regulation of the extracellular signal-regulated kin ase pathway in BCR signaling, because SHIP associates with Shc. We now report that SHIP-deficient DT40 B cells display enhanced Ca2+ mobiliz ation in response to BCR ligation, whereas extracellular signal-regula ted kinase activation is unaffected. This Ca2+ enhancement is due to a sustained intracellular Ca2+ increase or to long-lasting Ca2+ oscilla tions by loss of SHIP, as revealed by single-cell Ca2+ imaging analysi s. These results demonstrate the importance of SHIP in B cell activati on by the modulation of Ca2+ mobilization.