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TYRO protein tyrosine kinase binding protein

DAP12, KARAP, TYROBP
This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Multiple alternative transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Mar 2010] (from NCBI)
Top mentioned proteins: TREM2, CAN, V1a, DAP10, Syk
Papers on DAP12
Negative regulation of TLR signaling in myeloid cells-implications for autoimmune diseases.
Review
New
Buckner et al., Seattle, United States. In Immunol Rev, Jan 2016
This suggests that Lyp serves to downregulate a TLR inhibitory pathway in monocytes, and we propose that Lyp inhibits the TREM2/DAP12 inhibitory pathway.
Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.
New
Basbaum et al., San Francisco, United States. In Nat Neurosci, Jan 2016
Downstream of CSF1R, we found that the microglial membrane adaptor protein DAP12 was required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and the ensuing pain, but not for microglial proliferation.
The triggering receptor expressed on myeloid cells 2 - a molecular link of neuroinflammation and neurodegenerative diseases.
New
Walter, Bonn, Germany. In J Biol Chem, Jan 2016
UNASSIGNED: The triggering receptor expressed on myeloid cells (TREM) 2 is a member of the immunoglobulin superfamily of receptors and mediates signaling in immune cells via engagement of its co-receptor DNAX activating protein of 12 kDa (DAP12).
Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling.
New
Cai et al., Shanghai, China. In Aging Clin Exp Res, Jan 2016
CONCLUSIONS: A series of interactions, such as CSTA/TYROBP, CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of PMO.
Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.
New
Klesney-Tait et al., Iowa City, United States. In J Immunol, Jan 2016
Humans have two forms of TREM-1: a membrane receptor, associated with the adaptor DAP12, and a soluble receptor detected at times of infection.
A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts.
New
Nakamura et al., Oklahoma City, United States. In Clin Rev Allergy Immunol, Dec 2015
Receptor activator for NF-κB ligand (RANKL or TNFSF11), a tumor necrosis factor (TNF) superfamily member, is the master cytokine required for osteoclastogenesis with essential co-stimulatory signals mediated by immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptors, DNAX-associated protein 12 kDa size (DAP12) and FcεRI gamma chain (FcRγ).
What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic?
Review
New
Walker et al., Sun City, United States. In Neuroscience, Sep 2015
It pairs with the adaptor protein DNAX-activating protein of 12kDa (DAP12) to induce phagocytosis of apoptotic neurons without inflammatory responses, and to regulate Toll-like receptor-mediated inflammatory responses, and microglial activation.
NKG2D Receptor and Its Ligands in Host Defense.
Review
New
Lanier, San Francisco, United States. In Cancer Immunol Res, Jun 2015
In humans, NKG2D transmits signals by its association with the DAP10 adapter subunit, and in mice alternatively spliced isoforms transmit signals either using DAP10 or DAP12 adapter subunits.
TREM2 in CNS homeostasis and neurodegenerative disease.
Review
Bu et al., Jacksonville, United States. In Mol Neurodegener, 2014
The innate immune receptor and its adaptor protein—triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12)—possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways.
Triggering receptor expressed on myeloid cells receptor family modulators: a patent review.
Review
Agrawal et al., Omaha, United States. In Expert Opin Ther Pat, 2014
TREM-1 (CD354) and TREM-2 share the transmembrane adaptor DNAX-activation protein of 12 kDa (DAP12), but they possess separate stimulatory and inhibitory functional roles, especially in myeloid cells.
Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease.
Impact
Emilsson et al., New York City, United States. In Cell, 2013
Through an integrative network-based approach, we rank-ordered these network structures for relevance to LOAD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis, contains TYROBP as a key regulator, and is upregulated in LOAD.
Fyn positively regulates the activation of DAP12 and FcRγ-mediated costimulatory signals by RANKL during osteoclastogenesis.
GeneRIF
Choi et al., Ch'ŏngju, South Korea. In Cell Signal, 2012
Fyn relays RANK/RANKL signal to the costimulatory DAP12/FcRgamma-mediated signals.
Siglec-15 protein regulates formation of functional osteoclasts in concert with DNAX-activating protein of 12 kDa (DAP12).
GeneRIF
Takeya et al., Ikoma, Japan. In J Biol Chem, 2012
the Siglec-15-DAP12-Syk-signaling cascade plays a critical role in functional osteoclast formation.
Rat and mouse CD94 associate directly with the activating transmembrane adaptor proteins DAP12 and DAP10 and activate NK cell cytotoxicity.
GeneRIF
Dissen et al., Oslo, Norway. In J Immunol, 2012
Because mouse and rat NKG2C and -E transmembrane regions contain a positively charged arginine residue located close to the extracellular surface, these receptors may not associate with DAP12.
Siglecs and immune regulation.
Review
Impact
Mattoo et al., Boston, United States. In Annu Rev Immunol, 2011
This family also includes molecules involved in adhesion and phagocytosis and receptors that can associate with the ITAM-containing DAP12 adaptor.
Control of pathogenic CD4 T cells and lethal immunopathology by signaling immunoadaptor DAP12 during influenza infection.
GeneRIF
Xing et al., Hamilton, Canada. In J Immunol, 2011
we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection.
Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis.
GeneRIF
Belibasakis et al., Zürich, Switzerland. In Mol Immunol, 2011
the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells.
The structural basis for intramembrane assembly of an activating immunoreceptor complex.
Impact
Chou et al., Boston, United States. In Nat Immunol, 2010
Here we report the nuclear magnetic resonance (NMR) structure of the membrane-embedded, heterotrimeric assembly formed by association of the DAP12 signaling module with the natural killer (NK) cell-activating receptor NKG2C.
Indirect inhibition of Toll-like receptor and type I interferon responses by ITAM-coupled receptors and integrins.
Impact
Ivashkiv et al., New York City, United States. In Immunity, 2010
Induction of inhibitors was dependent on a pathway composed of signaling molecules DAP12, Syk, and Pyk2 that coupled to downstream kinases p38 and MSKs and required integration of IL-10-dependent and -independent signals.
Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils.
Impact
Lo-Man et al., Paris, France. In Immunity, 2009
We show here that after bacterial stimulation, and in contrast to monocytes and macrophages, murine neutrophils contributed poorly to inflammatory responses; however, they secreted high amounts of the anti-inflammatory cytokine IL-10 in a DAP12 adaptor-Syk kinase and MyD88 adaptor-dependent manner.
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