High impact information on CLEC4A

• These included various pattern recognition receptors, such as CD1b/c/e, TLR1, and C-type lectin superfamily member 6 [1].
• Among these, dendritic cell immunoreceptor (DCIR) induces negative signals through an inhibitory immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail [2].
• Thus, DCAR is closely related to DCIR, but it introduces activating signals into antigen-presenting cells through its physical and functional association with ITAM-bearing gamma chain [2].
• Here we identify a novel C-type lectin receptor, dendritic cell immunoactivating receptor (DCAR), whose extracellular lectin domain is highly homologous to that of DCIR [2].
• Unlike members of this complex, DCIR displays a typical lectin CRD rather than an NK cell type extracellular domain, and was expressed on DC, monocytes, macrophages, B lymphocytes, and granulocytes, but not detected on NK and T cells [3].

Biological context of CLEC4A

• The gene encoding human DCIR was localized to chromosome 12p13, in a region close to the NK gene complex [3].
• CLECSF6 bears the immunoreceptor tyrosine-based inhibition motif (ITIM) involved in signal transduction resulting in the inhibition of leukocyte activation [4].

Anatomical context of CLEC4A

• The ITIM in LLIR was demonstrated to bind SHP-1 in HL-60 cell after the tyrosine had been phosphorylated [5].
• This molecule, designated DCIR (for dendritic cell (DC) immunoreceptor), is a type II membrane glycoprotein of 237 aa with a single carbohydrate recognition domain (CRD), closest in homology to those of the macrophage lectin and hepatic asialoglycoprotein receptors [3].
• DCIR was mostly expressed by monocyte-related rather than Langerhans cell related DC obtained from CD34+ progenitor cells [3].
• The expression pattern of the ITIM-bearing lectin CLECSF6 in neutrophils suggests a key role in the control of inflammation [4].

Associations of CLEC4A with chemical compounds

• Although no ligand of DCIR has yet been identified, dectin-1 recognizes fungal beta-glucan and its critical role in the biological effects of beta-glucan has been vigorously investigated [6].

Other interactions of CLEC4A

• The surface expression of the CLECSF6 protein was reduced by TNF-alpha, IL-1alpha, LPS, and Matrigel [4].
• GM-CSF, IL-3, IL-4, and IL-13 caused an accumulation of the short CLECSF6 mRNA in neutrophils [4].
• We showed that a peptide bearing the ITIM of CLECSF6 in its phosphorylated form associates with both SHP-1 and SHP-2 [7].
• Granulocyte macrophage-colony stimulating factor reduces the affinity of SHP-2 for the ITIM of CLECSF6 in neutrophils: a new mechanism of action for SHP-2 [7].

Analytical, diagnostic and therapeutic context of CLEC4A

• Two alternatively spliced transmembraneless variants of LLIR were identified by RT-PCR and named as LLIRv1 and LLIRv2 [5].
• RT-PCR and immunoblotting analysis revealed that LLIR was expressed with much higher level in immature DC than in mature DC [5].
• Northern blot analysis showed DCIR mRNA to be predominantly transcribed in hematopoietic tissues [3].
• Although CLECSF6 has been the focus of the interest of many researchers lately, a Western blot characterization of the protein is still lacking [8].
• Sequence alignment and phylogenetic analysis of the CRD indicate that the protein has similarity with human dendritic cell immunoreceptor (DCIR), gp120 binding C-type lectin (gp120BCL) and mammalian hepatic lectins [9].

References