Table 1.
Myeloid C-type lectin receptors (CLRs) surveyed in this review.
Signaling module | Common name | Gene name | Source of flexible signaling | Signaling pathwaya | Flexibility outcomeb |
---|---|---|---|---|---|
No immunoreceptor tyrosine-based activating motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM) | DC-SIGN | CD209 | Homotetramerization | LSP1–KSR1–CNK–Raf-1 | Intrinsic (80) |
Sensing self and non-self | LSP1–IKKε–Bcl3 | Inhibitory (113–115) | |||
KSR1–CNK–Raf-1 | Activating (59, 110) | ||||
Heterologous modulation | (?) | Activating (148) | |||
Raf-1–MEK | Inhibitory (112) | ||||
Heterotrimerization DC-SIGN/MR/MDL-1 | DNAX-activation protein 12 (DAP12) | Activating (86) | |||
ITAM![]() |
MDL-1 | CLEC5A | Heterotrimerization DC-SIGN/MR/MDL-1 | DAP12 | Activating (86) |
Mannose receptor (MR) | MRC1 | Heterotrimerization DC-SIGN/MR/MDL-1 | DAP12 | Activating (86) | |
Inhibitory ITAM | Fc receptor γ (FcRγ)–Grb2−SHP-1 | Inhibitory (12) | |||
Dectin-2 | CLEC6A, Clec4n | Heterodimerization Dectin-2/MCL | FcRγ–spleen tyrosine kinase (Syk)–NF-κB p65 | Activating (85) | |
MCL | CLEC4D | Heterodimerization Mincle/MCL | FcRγ–Syk | Activating (81–84) | |
Mincle | CLEC4E | Heterodimerization Mincle/MCL | FcRγ–Syk | Activating (81–84) | |
Inhibitory ITAM | FcRγ–Syk–SHP-1 | Inhibitory (91, 92) | |||
Sensing self | Retarded Syk | Inhibitory (104, 105) | |||
FcRγ–Syk | Activating (7, 100–103) | ||||
Heterologous modulation | FcRγ−Syk | Activating (140, 141, 143) | |||
FcRγ−Syk–PKB–Mdm2 | Inhibitory (146) | ||||
hemITAM![]() |
CLEC-2 | CLEC1B | Homodimerization | Syk | Intrinsic (75, 76) |
DNGR-1 | CLEC9A | Motif context | Syk | Intrinsic (19, 60–64) | |
Dectin-1 | CLEC7A | Subcellular location | Syk | Intrinsic (67–70) | |
Ligand size-conditioned subcellular location | Syk–MAPK–reactive oxygen species | Intrinsic (71–74) | |||
Phosphatase association | SHP-1–PTEN–FcRγ SHIP-1 | Inhibitory (93, 94) | |||
SHP-2–Syk | Activating (95) | ||||
Heterologous modulation | Syk | Activating (124–126) | |||
PI3K–mTOR–HIF-1α | Activating (130–134) | ||||
Syk–Pyk2–ERK–SOCS-1 | Inhibitory (128) | ||||
ITIM![]() |
DCIR | CLEC4A, Clec4a2 | Activating ITIM | IFNI–STAT1 SHP-2 hijacking (?) | Activating (58) |
Sensing self and non-self | (?) | Activating (57) | |||
SHP-2/SHIP-1 | Inhibitory (108, 109) |
aDescribed in the indicated reference. In case it was not studied in depth, it might be incomplete.
bThis column indicates the inflammatory balance provided by each source of signaling flexibility. “Intrinsic” refers to specific responses triggered by particular CLRs.