Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling.
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 Fc gammaRIIB 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 Fc gammaRIIB.
Ono
M
M
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
Okada
H
H
Bolland
S
S
Yanagi
S
S
Kurosaki
T
T
Ravetch
J V
JV
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D005456:Fluorescent Dyes; D016257:Fura-2; D019204:GTP-Binding Proteins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D020559:Monomeric GTP-Binding Proteins; D015513:Oncogene Proteins / Q000502:physiology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D017452:Receptors, IgG / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D005456:Fluorescent Dyes; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr; D010744:Phosphoric Monoester Hydrolases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D019204:GTP-Binding Proteins; C490245:GEM protein, human; C088119:Gem protein, mouse; D020559:Monomeric GTP-Binding Proteins; D002118:Calcium; D016257:Fura-2