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TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1
Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB.. Science signaling, 2010-05-18
Topic: Brain proteins, microglia and lab models
The activation and fusion of macrophages and of osteoclasts require the adaptor molecule DNAX-activating protein of 12 kD (DAP12), which contains immunoreceptor tyrosine-based activation motifs (ITAMs). TREM2 (triggering receptor expressed on myeloid cells-2) is the main DAP12-associated receptor in osteoclasts and, similar to DAP12 deficiency, loss of TREM2 in humans leads to Nasu-Hakola disease, which is characterized by bone cysts and dementia. Furthermore, in vitro experiments have shown that deficiency in DAP12 or TREM2 leads to impaired osteoclast development and the formation of mononuclear osteoclasts.
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APA 7th
Peng, Q., Malhotra, S., Torchia, J. A., Kerr, W. G., Coggeshall, K. M., & Humphrey, M. B. (2010). TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling. https://doi.org/10.1126/scisignal.2000500
Vancouver
Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB. TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling. 2010. doi:10.1126/scisignal.2000500. PMID: 20484116.
BibTeX
@article{peng2010-20484116,
author = {Peng, Q. and Malhotra, S. and Torchia, J. A. and Kerr, W. G. and Coggeshall, K. M. and Humphrey, M. B.},
title = {{TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1}},
journal = {Science signaling},
year = {2010},
doi = {10.1126/scisignal.2000500},
pmid = {20484116},
url = {https://doi.org/10.1126/scisignal.2000500}
}
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Key findings
- TREM2 (triggering receptor expressed on myeloid cells-2) is the main DAP12-associated receptor in osteoclasts and, similar to DAP12 deficiency, loss of TREM2 in humans leads to Nasu-Hakola disease, which is characterized by bone cysts and dementia.
- Furthermore, in vitro experiments have shown that deficiency in DAP12 or TREM2 leads to impaired osteoclast development and the formation of mononuclear osteoclasts.
- Here, we demonstrate that the ligation of TREM2 activated phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase 1 (ERK1) and ERK2, and the guanine nucleotide exchange factor Vav3; induced the mobilization of intracellular calcium (Ca(2+)) and the reorganization of actin; and prevented apoptosis.
- The signaling adaptor molecule DAP10 played a key role in the TREM2- and DAP12-dependent recruitment of PI3K to the signaling complex.
Why it matters
This study describes how TREM2 and DAP12 activate PI3K signaling in osteoclasts, and notes that loss of TREM2 causes Nasu-Hakola disease with bone cysts and dementia. It is basic cell signaling work, not an Alzheimer's treatment.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science signaling) |
| Journal's citation record | 2 / 4 | Science Signaling: journal h-index 194 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 412 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.9 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 5.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 67 other studies in this library |
| Still being cited | 3 / 4 | Cited 131 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Mary Beth Humphrey: h-index 45 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20484116) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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