Human Type II Fcγ Receptors Inhibit B Cell Activation by Interacting with the p21 -dependent Pathway

Sármay, Gabriella; Koncz, Gábor; Gergely, J.

doi:10.1074/jbc.271.48.30499

Cited by 33 publications

(25 citation statements)

References 27 publications

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“…A drastic reduction of PIP 3 by SHIP upon Fc␥RIIB1 coaggregation with BCR has been shown to inhibit BCR-mediated Ca 2ϩ mobilization (24,25). In addition to its catalytic activity, SHIP functions as an adaptor molecule by binding Shc (17)(18)(19), which couples the BCR to the Grb2/Sos/Ras activation pathway (26), leading to MAP kinase activation in B cells (27,28). SHIP interaction with p62 dok , a RasGAP binding protein, has also been demonstrated.…”

mentioning

confidence: 99%

Effects of Src Homology Domain 2 (SH2)-Containing Inositol Phosphatase (SHIP), SH2-Containing Phosphotyrosine Phosphatase (SHP)-1, and SHP-2 SH2 Decoy Proteins on FcγRIIB1-Effector Interactions and Inhibitory Functions

Nakamura

Brauweiler

Cambier

2000

The Journal of Immunology

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Coaggregation of FcγRIIB1 with B cell Ag receptors (BCR) leads to inhibition of BCR-mediated signaling via recruitment of Src homology domain 2 (SH2)-containing phosphatases. In vitro peptide binding experiments using phosphotyrosine-containing sequences derived from the immunoreceptor tyrosine-based inhibitory motif (ITIM) known to mediate FcγRIIB1 effects suggest that the receptor uses SH2-containing inositol phophatase (SHIP) and SH2-containing phophotyrosine phosphatase (SHP)-1, as well as SHP-2 as effectors. In contrast, coimmunoprecipitation studies of receptor-effector associations suggest that the predominant FcγRIIB1 effector protein is SHIP. However, biologically significant interactions may be lost in such studies if reactants’ dissociation rates (Kd) are high. Thus, it is unclear to what extent these assays reflect the relative recruitment of SHIP, SHP-1, and SHP-2 to the receptor in vivo. As an alternative approach to this question, we have studied the effects of ectopically expressed SHIP, SHP-1, or SHP-2 SH2-containing decoy proteins on FcγRIIB1 signaling. Results demonstrate the SHIP is the predominant intracellular ligand for the phosphorylated FcγRIIB1 ITIM, although the SHP-2 decoy exhibits some ability to bind FcγRIIB1 and block Fc receptor function. The SHIP SH2, while not affecting FcγRIIB1 tyrosyl phosphorylation, blocks receptor-mediated recruitment of SHIP, SHIP phosphorylation, recruitment of p52 Shc, phosphatidylinositol 3,4,5-trisphosphate hydrolysis, inhibition of mitogen-activated protein kinase activation, and, albeit more modestly, FcγRIIB1 inhibition of Ca2+ mobilization. Taken together, results implicate ITIM interactions with SHIP as a major mechanism of FcγRIIB1-mediated inhibitory signaling.

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confidence: 99%

Effects of Src Homology Domain 2 (SH2)-Containing Inositol Phosphatase (SHIP), SH2-Containing Phosphotyrosine Phosphatase (SHP)-1, and SHP-2 SH2 Decoy Proteins on FcγRIIB1-Effector Interactions and Inhibitory Functions

Nakamura

Brauweiler

Cambier

2000

The Journal of Immunology

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“…ITIM-bearing molecules, such as Fc␥RIIB (34,35,40,41), can interrupt signal transduction and ultimately inhibit antibody production (17,31,49). For example, measles virus, a notorious agent for suppression of antibody production (10,36,50), binds to human Fc␥RIIB, which is functionally related to CEACAM1 (15), and inhibits human B-cell antibody production (45).…”

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confidence: 99%

Neisseria gonorrhoeaeKills Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 (CD66a)-Expressing Human B Cells and Inhibits Antibody Production

et al. 2005

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“…In addition, SHIP has been implicated in inhibitory signaling induced by Fc␥RIIB, the B cell receptor for the Fc portion of soluble IgG. Co-crosslinking of the Fc␥RIIB with the BCR inhibits B cell proliferation, Ras activation, and the influx of calcium across the cell membrane normally observed after BCR stimulation (31)(32)(33)(34). SHIP binds to the cytoplasmic tail of the Fc␥RIIB after its co-ligation with the BCR (35,36) and has been shown to inhibit sustained influx of calcium into the cell (37).…”

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confidence: 99%

The Src Homology Domain 2-Containing Inositol Phosphatase SHIP Forms a Ternary Complex with Shc and Grb2 in Antigen Receptor-stimulated B Lymphocytes

Harmer¹,

DeFranco

1999

Journal of Biological Chemistry

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The inositol phosphatase SHIP has been implicated in signaling events downstream of a variety of receptors and is thought to play an inhibitory role in stimulated B cells. We and others have reported that SHIP is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR) cross-linking and forms a complex with the adapter protein Shc. Here, we report that cross-linking of the BCR induces association between Grb2 and SHIP as well as association between Shc and SHIP. We made use of a Grb2-deficient B cell line to demonstrate both in vitro and in vivo that Grb2 expression is required for the efficient association between Shc and SHIP. The results indicate that SHIP, Shc, and Grb2 form a ternary complex in stimulated B cells, with Grb2 stabilizing the interaction between Shc and SHIP. The interactions between Shc, Grb2, and SHIP are therefore analogous to the interactions between Shc, Grb2, and SOS. Shc and Grb2 may help to localize SHIP to the cell membrane, regulating SHIP's inhibitory function following BCR stimulation.

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Human Type II Fcγ Receptors Inhibit B Cell Activation by Interacting with the p21 -dependent Pathway

Cited by 33 publications

References 27 publications

Effects of Src Homology Domain 2 (SH2)-Containing Inositol Phosphatase (SHIP), SH2-Containing Phosphotyrosine Phosphatase (SHP)-1, and SHP-2 SH2 Decoy Proteins on FcγRIIB1-Effector Interactions and Inhibitory Functions

Effects of Src Homology Domain 2 (SH2)-Containing Inositol Phosphatase (SHIP), SH2-Containing Phosphotyrosine Phosphatase (SHP)-1, and SHP-2 SH2 Decoy Proteins on FcγRIIB1-Effector Interactions and Inhibitory Functions

Neisseria gonorrhoeaeKills Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 (CD66a)-Expressing Human B Cells and Inhibits Antibody Production

The Src Homology Domain 2-Containing Inositol Phosphatase SHIP Forms a Ternary Complex with Shc and Grb2 in Antigen Receptor-stimulated B Lymphocytes

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