Search results for CLEC4E

Showing 16 results out of 18

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Protein (1 results from a total of 1)

Identifier: R-HSA-2130735
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: CLEC4E: Q9ULY5

Reaction (6 results from a total of 6)

Identifier: R-HSA-5621354
Species: Homo sapiens
Compartment: plasma membrane
CLEC4E (also called Mincle or CLECSF9) is a C-type lectin receptor (CLR) expressed in activated macrophages and dendritic cells (DCs) in response to several inflammatory stimuli, including LPS, TNF, IL6, IFN-gamma and cellular stresses (Matsumoto et al. 1999). Like the other activating receptors in the Dectin-2 family, CLEC4E is coupled with the FCERG (High affinity immunoglobulin epsilon receptor subunit gamma) to transduce intracellular signalling (Yamasaki et al. 2008). CLEC4E possesses a typical carbohydrate recognition domain (CRD) containing an EPN (Glu-Pro-Asn) motif which is capable of recognising several types of carbohydrates, particularly those containing alpha-mannose. CLEC4E can recognise fungal (Candida albicans and Malassezia), mycobacterial (trehalose-6,6?-dimycolate (TDM)) and necrotic cell ligands implicating this receptor in anti-microbial immunity and homeostasis (Schoenen et al. 2010, Yamasaki et al. 2009, Graham & Brown. 2009).
Identifier: R-HSA-5621355
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Ligation of CLEC6A (C-type lectin domain family 6 member A/Dectin-2) and CLEC4E (Mincle) with their appropriate ligands trigger the tyrosine phosphorylation of the immune receptor tyrosine-based activation motif (ITAM) in the cytoplasmic tail of FCER1G chain. Tyrosine Y65 and Y76 in the ITAM are phosphorylated and this phosphorylation is mediated by Src kinases Lyn and Fyn (Sato et al. 2006, Yamasaki et al. 2008, Quek et al. 1998).
Identifier: R-HSA-5621363
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Activation of SYK triggers multiple cascades, which induces NF-kB activation through a CARD9-dependent pathway. Phospholipase C-gamma 2 (PLCG2) is one of the key signaling components of the CLEC4E (Mincle)/CLEC6A (Dectin-2) pathway that connects SYK activation to CARD9 recruitment. PLCG2 is activated upon CLEC4E (Mincle)/CLEC6A (Dectin-2) engagement and triggers an intracellular Ca2+ flux. SYK and Src family kinases are upstream of PLCG2. SYK phosphorylates PLCG2 on Y753 and Y759, enhancing the activity of PLCG2 (Gorjestani et al. 2011, Suzuki-Inoue et al. 2004).
Identifier: R-HSA-5621353
Species: Homo sapiens
Compartment: plasma membrane
CLEC4D (Macrophage C-type lectin (MCL)) is a member of the C-type lectin that recognises mycobacterial trehalose-6,6'-dimycolate (TDM) or cord factor likely to arise from gene duplication of CLEC4E (also called Minicle). CLEC4D is constitutively expressed on myeloid cells. It couples with FCERG (High affinity immunoglobulin epsilon receptor subunit gamma) and acts as an activating receptor (Miyake et al. 2013).
Identifier: R-HSA-5607734
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Protein kinase C-delta (PRKCD), activated upon CLEC7A (Dectin-1)-SYK signaling, phosphorylates CARD9 leading to NF-kB activation (Strasser et al. 2012) and complex formation between CARD9 and BCL10. CLEC6A (Dectin-2) and CLEC4E (Mincle) also induces intracellular signaling through PRKCD and CARD9-BCL10-MALT1 pathway. Similar to the CLEC7A responses, both CLEC6A and CLEC4E-induced interleukin 10 (IL10) and tumour necrotic factor (TNF) production were severely impaired in the absence of PRKCD (Strasser et al. 2012). PRKCD is a member of the Ca2+ independent and diacylglycerol (DAG) dependent novel PKC subfamily. PKC family members exist in an immature inactive conformation that requires post-translational modifications to achieve catalytic maturity. The catalytic maturation of PRKCD involves the auto-phosphorylation of Ser645 and the phosphorylation of Thr507 and Ser664 (Li et al. 1997, Keranen et al. 1995). These phosphorylations of activation loop residues act as a priming step that allows the catalytic maturation of PRKCD (Dutil et al. 1998). Fully phosphorylated and primed PRKCD localises to the cytosol with its pseudosubstrate occupying the substrate-binding cavity. Signals that cause the lipid hydrolysis recruit PKC to membranes. The C1 domain in PRKCD is a cysteine-rich compact structure, identified as the interaction site for DAG and phorbol ester. PRKCD preferentially translocates to the plasma membrane (Stahelin et al. 2004, Newton 2010).
Identifier: R-HSA-5607740
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Activation of NF-kB signaling is a critical event downstream of CLEC7A (Dectin-1), CLEC6A (Dectin-2) (Bi et al. 2010) and CLEC4E (Mincle) (Yamasaki et al. 2008), requiring the adapter protein Caspase recruitment domain (CARD)-containing protein 9 (CARD9) in dendritic cells and in macrophages (Gross et al. 2006, Hara et al. 2007). CARD9 is analogous to CARD-containing MAGUK protein 1 (CARMA1), which mediates T-cell receptor (TCR) activation of NF-kB in lymphocytes. CARD9 is downstream of SYK and becomes phosphorylated by PRKCD (Protein kinase C-delta) phosphorylates CARD9 on Thr-231 (T231), which is required for the signal-induced association of CARD9 with B-cell lymphoma 10 (BCL10) and Mucosa-associated lymphoid tissue 1 (MALT1) and the subsequent recruitment of MAP3K transforming growth factor beta activated kinase 1 (TAK1), leading to activation of the NF-kB pathway (Strasser et al. 2012). A homozygous loss-of-function mutation in human CARD9 results in a premature termination codon (Gln295*). Patients with this mutation are highly susceptible to fungal infections (Glocker et al. 2009).

Complex (6 results from a total of 8)

Identifier: R-HSA-5621137
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621144
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621142
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621157
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621160
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621133
Species: Homo sapiens
Compartment: plasma membrane

Set (2 results from a total of 2)

Identifier: R-HSA-5621130
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5621145
Species: Homo sapiens
Compartment: plasma membrane

Pathway (1 results from a total of 1)

Identifier: R-HSA-5621480
Species: Homo sapiens
Compartment: plasma membrane
Dendritic cell-associated C-type lectin-2 (Dectin-2) family of C-type lectin receptors (CLRs) includes Dectin-2 (CLEC6A), blood dendritic antigen 2 (BDCA2/CLEC4C), macrophage C-type lectin (MCL/CLEC4D), Dendritic cell immunoreceptor (DCIR/CLEC4A) and macrophage inducible C-type lectin (Mincle/CLEC4E). These receptors possesses a single extracellular conserved C-type lectin domain (CTLD) with a short cytoplasmic tail that induces intracellular signalling indirectly by binding with the FCERG (High affinity immunoglobulin epsilon receptor subunit gamma) except for DCIR that has a longer cytoplasmic tail with an integral inhibitory signalling motif (Graham & Brown. 2009, Kerschera et al. 2013). CLEC6A (Dectin-2) binds to high mannose containing pathogen-associated molecular patterns (PAMPs) expressed by fungal hyphae, and CLEC4E (mincle) binds to alpha-mannaosyl PAMPs on fungal, mycobacterial and necrotic cell ligands. Both signaling pathways lead to Toll-like receptor (TLR)-independent production of cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL6). Similarities with Dectin-1 (CLC7A) signaling pathway suggests that both these CLRs couple SYK activation to NF-kB activation using a complex involving CARD9, BCL10 and MALT1 (Geijtenbeek & Gringhuis 2009).
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