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A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages
Peng Q, Long CL, Malhotra S, Humphrey MB.. Science signaling, 2013-08-20
Topic: Brain proteins, microglia and lab models
DNAX-activating protein of 12 kD (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein found in myeloid cells and natural killer cells, and it couples to various receptors that mediate either cellular activation or inhibition. DAP12 inhibits Toll-like receptor (TLR) signaling, such as that of TLR4 in response to its ligand lipopolysaccharide (LPS), as well as cytokine responses by coupling to TREM2 (triggering receptor expressed on myeloid cells 2) at the plasma membrane. Understanding the mechanisms that inhibit inflammatory responses in macrophages is important for the development of therapies to treat inflammatory diseases.
Key findings
- DAP12 inhibits Toll-like receptor (TLR) signaling, such as that of TLR4 in response to its ligand lipopolysaccharide (LPS), as well as cytokine responses by coupling to TREM2 (triggering receptor expressed on myeloid cells 2) at the plasma membrane.
- Understanding the mechanisms that inhibit inflammatory responses in macrophages is important for the development of therapies to treat inflammatory diseases.
- We show that inhibition of LPS responses by DAP12 is mediated by the adaptor protein DOK3 (downstream of kinase 3).
- DOK3 physically associated with the ITAM of DAP12 through its phosphotyrosine-binding domain.
Why it matters
This laboratory study in macrophages showed that a physical interaction between DOK3 and DAP12 is needed to inhibit lipopolysaccharide signaling. It is basic cell research and does not show a treatment or cure for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 | 2013 — 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 | 4 / 7 | Cited 62 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.1 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 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 | 1 / 3 | Veterans Health Administration: institution h-index 968 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23962980) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Peng, Q., Long, C. L., Malhotra, S., & Humphrey, M. B. (2013). A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages. Science signaling. https://doi.org/10.1126/scisignal.2003801
Vancouver
Peng Q, Long CL, Malhotra S, Humphrey MB. A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages. Science signaling. 2013. doi:10.1126/scisignal.2003801. PMID: 23962980.
BibTeX
@article{peng2013-23962980,
author = {Peng, Q. and Long, C. L. and Malhotra, S. and Humphrey, M. B.},
title = {{A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages}},
journal = {Science signaling},
year = {2013},
doi = {10.1126/scisignal.2003801},
pmid = {23962980},
url = {https://doi.org/10.1126/scisignal.2003801}
}
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