The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcγ receptors FcγRIIB and FcγRIIA

Huang, Zhenyu; Hunter, Sharon; Kim, Moo‐Kyung; Indik, Zena K.; Schreiber, Alan D.

doi:10.1189/jlb.0902454

Cited by 86 publications

(79 citation statements)

References 30 publications

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“…SHIP-1 was first shown to associate with immunoreceptor tyrosine-based inhibitory motifs of inhibitory FcRIIB, which indicated that it normally inhibits phagocytosis [92]. SHIP-1 has recently been shown to associate with FcR containing ITAMs [17,93]; it is therefore possible that it contributes to phagosome formation by turning off PI(3,4,5)P 3 -dependent signals in the forming phagosome.…”

Section: Phagosomal Lipidsmentioning

confidence: 99%

“…Syk signaling is required for efficient phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI-3K) [14], which activates the PI-3K catalytic subunit p110␤ [15], generating PI-3,4,5-trisphosphate [PI(3,4,5)P 3 ] from PI-4,5-bisphosphate [PI(4,5)P 2 ] in the membrane near the receptor complex. Other proteins recruited to the FcR complex include the protein phosphatase Src homology 2 (SH2)-containing tyrosine phosphatase-1 [16,17], Gab2 [18], SH2 domain-containing leukocyte phosphoprotein of 76 kDa [19], Cbl, Nck [20], and the 5Ј PI phosphatase, SH2 domain-containing inositol phosphatase 1 (SHIP-1) [17,21].…”

Section: Fcr and Associated Proteinsmentioning

confidence: 99%

“…Some of the many isoforms of membrane lipid-modifying enzymes contribute to FcR-mediated phagocytosis, including PI4P5K [34], PI-3K [67], PLA 2 [68], PLC [34], PLD [69], phosphatase and tensin homology deleted on chromosome 10 (PTEN) [70,71], and SHIP-1 [17,21]. The products of these enzymes can influence the activities of essential regulatory proteins [72].…”

Section: Phagosomal Lipidsmentioning

confidence: 99%

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The coordination of signaling during Fc receptor-mediated phagocytosis

Swanson

Hoppe

2004

Journal of Leukocyte Biology

275

234

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Section: Phagosomal Lipidsmentioning

confidence: 99%

Section: Fcr and Associated Proteinsmentioning

confidence: 99%

Section: Phagosomal Lipidsmentioning

confidence: 99%

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The coordination of signaling during Fc receptor-mediated phagocytosis

Swanson

Hoppe

2004

Journal of Leukocyte Biology

275

234

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“…This reduces the ability of certain pleckstrin homology-containing proteins involved in mediating activation signals to target to the plasma membrane and become activated (14). Although SHIP1 has been studied extensively in the context of inhibitory FcRs (15,16), its role in NK cell responses initiated by the activation of FcgRIIIa is less well understood. Of note, Galandrini et al (17,18) have shown that FcgRIIIa cross-linking on primary human NK cells induced transient translocation of SHIP1 into lipid raft microdomains, where it associated with the~-chain of the FcR complex and negatively regulated antibody-dependent cellular cytotoxicity (ADCC).…”

Section: Introductionmentioning

confidence: 99%

Src Homology 2–Containing Inositol 5′-Phosphatase 1 Negatively Regulates IFN-γ Production by Natural Killer Cells Stimulated with Antibody-Coated Tumor Cells and Interleukin-12

Parihar¹,

Trotta²,

Roda³

et al. 2005

Cancer Research

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We have previously shown that natural killer (NK) cells secrete a distinct profile of immunomodulatory cytokines in response to dual stimulation with antibody-coated tumor cells and interleukin-12 (IL-12). This NK cell cytokine response is dependent on synergistic signals mediated by the activating receptor for the Fc portion of IgG (Fc;RIIIa) and the IL-12 receptor (IL-12R), both constitutively expressed on NK cells. The phosphatase Src homology 2-containing inositol 5V -phosphatase 1 (SHIP1) is known to exert inhibitory effects on Fc receptor (FcR) signaling via its enzymatic activity on phosphatidylinositol 3-kinase (PI3-K) products within many cells of the immune system, most notably mast cells, B cells, and monocytes. However, its activity in the context of FcR activation on NK cells has not been fully explored. The current study focused on the regulation of Fc;RIIIa-induced NK cell cytokine production by SHIP1. Inhibitor studies showed that NK cell IFN-; production following FcR stimulation in the presence of IL-12 depended, in part, on the downstream products of PI3-K. Overexpression of wild-type (WT) SHIP1, but not a catalytic-deficient mutant, via retroviral transfection of primary human NK cells, resulted in a >70% reduction of NK cell IFN-; production in response to costimulation. In addition, NK cells from SHIP1

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“…SHP-1, which is mainly expressed in hematopoietic and less in epithelial cells, predominantly acts as a negative regulator of cellular signaling pathways induced by transmembrane receptors such as EpoR, c-Kit, and Fc␥RIIb1 (5)(6)(7)(8). In contrast, the ubiquitous SHP-2 is a positive regulator in the signal transduction of receptors like insulin receptor, platelet-derived growth factor receptor and EpoR (2)(3)(4)9).…”

mentioning

confidence: 99%

Sequence Specificity of SHP-1 and SHP-2 Src Homology 2 Domains

Imhof

Wavreille

May

et al. 2006

Journal of Biological Chemistry

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A combinatorial phosphotyrosyl (pY) peptide library was screened to determine the amino acid preferences at the pY؉4 to pY؉6 positions for the four SH2 domains of protein-tyrosine phosphatases SHP-1 and SHP-2. Individual binding sequences selected from the library were resynthesized and their binding affinities and specificities to various SH2 domains were further evaluated by SPR studies, stimulation of SHP-1 and SHP-2 phosphatase activity, and in vitro pulldown assays. These studies reveal that binding of a pY peptide to the N-SH2 domain of SHP-2 is greatly enhanced by a large hydrophobic residue (Trp, Tyr, Met, or Phe) at the pY؉4 and/or pY؉5 positions, whereas binding to SHP-1 N-SH2 domain is enhanced by either hydrophobic or positively charged residues (Arg, Lys, or His) at these positions. Similar residues at the pY؉4 to pY؉6 positions are also preferred by SHP-1 and SHP-2 C-SH2 domains, although their influence on the overall binding affinities is much smaller compared with the N-SH2 domains. A structural model was generated to qualitatively interpret the contribution of the pY؉4 and pY؉5 residues to the overall binding affinity. Examination of pY motifs from known SHP-1 and SHP-2-binding proteins shows that many of the pY motifs contain a hydrophobic or positively charged residue(s) at the pY؉4 and pY؉5 positions. Src homology 2 (SH2)4 domains are ϳ100-amino acid protein modules that are present in a wide variety of proteins. These domains mediate protein-protein interactions by recognizing phosphorylated tyrosine (pY) residues in proteins and play many different roles in intracellular signaling pathways (1). Protein-tyrosine phosphatases SHP-1 and SHP-2 have two adjacent SH2 domains (termed N-SH2 and C-SH2). The two enzymes share highly similar sequences and three-dimensional structures, and yet they have quite different functions in vivo (2-4). SHP-1, which is mainly expressed in hematopoietic and less in epithelial cells, predominantly acts as a negative regulator of cellular signaling pathways induced by transmembrane receptors such as EpoR, c-Kit, and Fc␥RIIb1 (5-8). In contrast, the ubiquitous SHP-2 is a positive regulator in the signal transduction of receptors like insulin receptor, platelet-derived growth factor receptor and EpoR (2-4, 9). The association of the N-SH2 domain of SHP-1 or SHP-2 with an activated receptor results in the stimulation of their phosphatase activity. Indeed, both phosphatases exist in an inactive form in the cytosol, with the N-SH2 domain occluding the substrate-binding pocket of the PTP domain. The occupation of the N-SH2 domain with a phosphotyrosine-containing ligand leads to the dissociation of the inactive N-SH2⅐PTP complex and subsequently to the activation of the enzymes (10 -12).Specific association of an SH2 domain with a cognate pY protein is mediated by the peptide motif surrounding the pY residue. It has been assumed that for most SH2 domains, sequence specificity is dictated by the three residues immediately C-terminal to pY (position ϩ1 to ϩ3 relative to p...

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The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcγ receptors FcγRIIB and FcγRIIA

Cited by 86 publications

References 30 publications

The coordination of signaling during Fc receptor-mediated phagocytosis

The coordination of signaling during Fc receptor-mediated phagocytosis

Src Homology 2–Containing Inositol 5′-Phosphatase 1 Negatively Regulates IFN-γ Production by Natural Killer Cells Stimulated with Antibody-Coated Tumor Cells and Interleukin-12

Sequence Specificity of SHP-1 and SHP-2 Src Homology 2 Domains

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