Deletion of SHIP or SHP-1 Reveals Two Distinct Pathways for Inhibitory Signaling

• Published in: Cell 1997-07, Vol.90 (2), p.293-301
• Main Authors: Ono, Masao, Okada, Hidetaka, Bolland, Silvia, Yanagi, Shigeru, Kurosaki, Tomohiro, Ravetch, Jeffrey V
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Antigens, CD - metabolism; Apoptosis - physiology; B-Lymphocytes - chemistry; B-Lymphocytes - cytology; B-Lymphocytes - enzymology; Calcium - metabolism; Cells, Cultured; Chickens; Fluorescent Dyes; Fura-2; GTP-Binding Proteins - metabolism; Immediate-Early Proteins - metabolism; Intracellular Signaling Peptides and Proteins; Mice; Monomeric GTP-Binding Proteins; Oncogene Proteins - physiology; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - immunology; Phosphoric Monoester Hydrolases - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - immunology; Protein Tyrosine Phosphatases - metabolism; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcr; Receptors, IgG - metabolism; SH2 Domain-Containing Protein Tyrosine Phosphatases; Signal Transduction - physiology; src Homology Domains - genetics; src Homology Domains - immunology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80337-2

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.