title: Protein-tyrosine phosphatase SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of B cell antigen receptor activation.
abstract: The inhibitory Fc receptor, FcgammaRIIB, provides a signal that aborts B cell antigen receptor activation, blocking extracellular calcium influx. Because the protein-tyrosine phosphatase SHP-1 binds tyrosyl phosphorylated FcgammaRIIB and FcgammaRIIB-mediated inhibition is defective in motheaten (me/me) mice, which do not express SHP-1, it was proposed that SHP-1 mediates FcgammaRIIB signaling in B cells (D'Ambrosio, D., Hippen, K. L., Minskoff, S. A., Mellman, I., Pani, G., Siminovitch, K. A., and Cambier, J. C. (1995) Science 268, 293-297). However, SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of FcepsilonRI signaling in mast cells (Ono, M., Bolland, S., Tempst, P., and Ravetch, J. V. (1996) Nature 383, 263-266), prompting us to re-examine the role of SHP-1 in FcgammaRIIB signaling in B cells. We generated immortalized sIgM+, FcgammaRIIB+ cell lines from me/me mice and normal littermates. Co-ligation of FcgammaRIIB and the sIgM antigen receptor inhibits calcium influx in both cell lines. Inhibition is reversed by preincubation with anti-FcgammaRIIB antibodies, indicating that it is mediated by FcgammaRIIB. The inositol 5' phosphatase SHIP is recruited to tyrosyl-phosphorylated FcgammaRIIB in both cell lines. FcgammaRIIB-mediated CD19 dephosphorylation also occurs in the presence or the absence of SHP-1. Our results establish that SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of sIgM antigen receptor signaling.
authors.affiliation: Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. mnadler@bidmc.harvard.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Nadler
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: J S
authors.initials: JS
authors.lastname: Anderson
authors.forename: H H
authors.initials: HH
authors.lastname: Wortis
authors.forename: B G
authors.initials: BG
authors.lastname: Neel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors*; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; C080571:Fc gamma receptor IIB; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D014443:Tyrosine; 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; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D002118:Calcium