Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling

Ono Masao, Hidetaka Okada, Silvia Bolland, Shigeru Yanagi, Tomohiro Kurosaki, Jeffrey V. Ravetch

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390 Citations (Scopus)

Abstract

Two signaling molecules have been implicated in the modulation of immune receptor activation by inhibitory coreceptors: an inositol polyphosphate 5'- phosphatase, SHIP, and a tyrosine phosphatase, SHP-1. To address the necessity, interaction, or redundancy of these signaling molecules, we have generated SHP-1-or SHIP-deficient B cell lines and determined their ability to mediate inhibitory signaling. Two distinct classes of inhibitory responses are defined, mediated by the selective recruitment of SHP-1 or SHIP. The FcγRIIB class of inhibitory signaling is dependent on SHIP and not SHP-1; conversely, the KIR class requires SHP-1 and not SHIP. The consequence of this selective recruitment by inhibitory receptor engagement is seen in BCR- triggered apoptosis. SHP-1-mediated inhibitory signaling blocks apoptosis, while SHIP recruitment attenuates a proapoptotic signal initiated by FcγRIIB.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalCell
Volume90
Issue number2
DOIs
Publication statusPublished - 1997 Jul 25
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Masao, O., Okada, H., Bolland, S., Yanagi, S., Kurosaki, T., & Ravetch, J. V. (1997). Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell, 90(2), 293-301. https://doi.org/10.1016/S0092-8674(00)80337-2