The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcγ receptors FcγRIIB and FcγRIIA
Abstract
Inositol and tyrosine phosphatases have been implicated in inhibitory signaling by an Fc receptor for immunoglobulin G, FcgammaRIIB, in B cells, mast cells, and monocytes. Here, we propose a role for the Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) in FcgammaRIIB-mediated inhibition of FcgammaR signaling. Coexpression of SHP-1 enhances FcgammaRIIB-mediated inhibition of FcgammaRIIA phagocytosis in COS-1 cells. SHP-1 also enhances the reduction in FcgammaRIIA tyrosine phosphorylation that accompanies this inhibition. Significantly, tyrosine phosphorylation of Syk kinase is substantially inhibited by SHP-1. Furthermore, the activation of SHP-1 tyrosine phosphorylation is observed following stimulation of FcgammaRII in COS-1 cells and in human monocytes. The SH2 domain containing inositol phosphatase (SHIP), SHIP-1 also enhances FcgammaRIIB-mediated inhibition of FcgammaRIIA, indicating that FcgammaRIIB can use more than one pathway for its inhibitory action. In addition, SHP-1 and SHIP-1 can inhibit FcgammaRIIA phagocytosis and signal transduction in the absence of FcgammaRIIB. The data support emerging evidence that SH2-containing phosphatases, such as SHP-1 and SHIP-1, can modulate signaling by "activating" receptors.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SHIP1 directly inhibits FCγRIIA by binding to its ITAM, which prevents activation of PI3K.
“SHIP1 also was shown to directly inhibit FCγRIIA by binding to its ITAM (Fig. 3C), which prevents the activation of PI3K [134, 137–140].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [137]
In mouse macrophages and COS cells, SHIP1 activates the ITIM of the inhibitory receptor FCγRIIβ, which inhibits the activating receptor FCγRIIA to block FCγRIIA-mediated phagocytosis.
“In mouse macrophages and COS cells, SHIP1 was shown to activate the ITIM of the inhibitory receptor FCγRIIβ, which inhibits the activating receptor FCγRIIA to block FCγRIIA-mediated phagocytosis (Fig. 3C).”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [137]
Cited by
Sorted by citations
Genetics ignite focus on microglial inflammation in Alzheimer’s disease
Malik, M., Parikh, I., Vasquez, J. B., Smith, C., Tai, L., Bu, G., LaDu, M. J., Fardo, D. W., Rebeck, G. W., & Estus, S. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0048-1 · Cited by 161 · see citing works
Terzioglu, G., & Young-Pearse, T. L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00674-9 · Cited by 95 · see citing works
Ming‐Lum, A., Shojania, S., So, E., McCarrell, E., Shaw, E., Vu, D., Wang, I., McIntosh, L. P., & Mui, A. L. ‐. (2012) · The FASEB Journal · doi:10.1096/fj.11-201475 · Cited by 34 · see citing works
- Authors
- Huang, Z.-Y., Hunter, S., Kim, M.-K., Indik, Z. K., & Schreiber, A. D.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Schreiber, Alan D
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-06-01
- Volume
- 73
- Issue
- 6
- Pages
- 823-829
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2334505016
- Cited by
- 105
- References
- 0
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 1 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 10 · 2014: 5 · 2013: 3 · 2012: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (A1-2193, HL 69498)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- SHP-1, SHIP1, FcγRIIB, FcγRIIa, Fc gamma receptor, inhibitory signaling, protein tyrosine phosphatase, inositol phosphatase, Syk, tyrosine phosphorylation, phagocytosis, monocytes, B cells, mast cells, ITIM, ITAM, receptor tyrosine kinase signaling
- MeSH terms
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, Syk Kinase, Animals, Cells, Cultured, Enzyme Precursors, Humans, Monocytes, Phagocytosis, Phosphoric Monoester Hydrolases, Phosphorylation, Protein-Tyrosine Kinases, Tyrosine, Signal Transduction, Antigens, CD, Protein Tyrosine Phosphatases, Receptors, IgG, COS Cells, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Phosphatase 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
