KEGG   PATHWAY: mmu04625
Entry
mmu04625                    Pathway                                
Name
C-type lectin receptor signaling pathway - Mus musculus (house mouse)
Description
C-type lectin receptors (CLRs) are a large superfamily of proteins characterized by the presence of one or more C-type lectin-like domains (CTLDs). CLRs function as pattern-recognition receptors (PRRs) for pathogen-derived ligands in dendric cells, macrophages, neutrophils, etc., such as Dectin-1 and Dectin-2 for recognition of fungi-derived B-glucan and high mannose-type carbohydrates. Upon ligand binding, CLRs stimulate intracellular signaling cascades that induce the production of inflammatory cytokines and chemokines, consequently triggering innate and adaptive immunity to pathogens.
Class
Organismal Systems; Immune system
Pathway map
mmu04625  C-type lectin receptor signaling pathway
mmu04625

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
56644  Clec7a; C-type lectin domain family 7, member a [KO:K10074]
16985  Lsp1; lymphocyte specific 1 [KO:K14957]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
17532  Mras; muscle and microspikes RAS [KO:K07831]
20130  Rras; related RAS viral (r-ras) oncogene [KO:K07829]
66922  Rras2; related RAS viral (r-ras) oncogene 2 [KO:K07830]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
19698  Relb; avian reticuloendotheliosis viral (v-rel) oncogene related B [KO:K09253]
16159  Il12a; interleukin 12a [KO:K05406]
16160  Il12b; interleukin 12b [KO:K05425]
16176  Il1b; interleukin 1 beta [KO:K04519]
20963  Syk; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
19247  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
53859  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
18034  Nfkb2; nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100 [KO:K04469]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
12313  Calm1; calmodulin 1 [KO:K02183]
80796  Calm4; calmodulin 4 [KO:K02183]
12315  Calm3; calmodulin 3 [KO:K02183]
12314  Calm2; calmodulin 2 [KO:K02183]
70405  Calml3; calmodulin-like 3 [KO:K02183]
494124  Calm5; calmodulin 5 [KO:K02183]
75600  Calml4; calmodulin-like 4 [KO:K02183]
19057  Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19055  Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19058  Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
18018  Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
18019  Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18021  Nfatc3; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 3 [KO:K17333]
73181  Nfatc4; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4 [KO:K17334]
16183  Il2; interleukin 2 [KO:K05429]
16153  Il10; interleukin 10 [KO:K05443]
13654  Egr2; early growth response 2 [KO:K12496]
13655  Egr3; early growth response 3 [KO:K12497]
19225  Ptgs2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
18753  Prkcd; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
216799  Nlrp3; NLR family, pyrin domain containing 3 [KO:K12800]
66824  Pycard; PYD and CARD domain containing [KO:K12799]
12362  Casp1; caspase 1 [KO:K01370] [EC:3.4.22.36]
332579  Card9; caspase recruitment domain family, member 9 [KO:K12794]
12042  Bcl10; B cell leukemia/lymphoma 10 [KO:K07368]
240354  Malt1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
12370  Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
21926  Tnf; tumor necrosis factor [KO:K03156]
16193  Il6; interleukin 6 [KO:K05405]
83430  Il23a; interleukin 23, alpha subunit p19 [KO:K05426]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
16476  Jun; jun proto-oncogene [KO:K04448]
208650  Cblb; Casitas B-lineage lymphoma b [KO:K22517] [EC:2.3.2.27]
56620  Clec4n; C-type lectin domain family 4, member n [KO:K17514]
381809  Clec4b2; C-type lectin domain family 4, member b2 [KO:K17514]
69810  Clec4b1; C-type lectin domain family 4, member b1 [KO:K17514]
14127  Fcer1g; Fc receptor, IgE, high affinity I, gamma polypeptide [KO:K07983]
170776  Cd209c; CD209c antigen [KO:K06563]
170779  Cd209d; CD209d antigen [KO:K06563]
170780  Cd209e; CD209e antigen [KO:K06563]
170786  Cd209a; CD209a antigen [KO:K06563]
69165  Cd209b; CD209b antigen [KO:K06563]
69142  Cd209f; CD209f antigen [KO:K06563]
70192  Cd209g; CD209g antigen [KO:K06563]
69632  Arhgef12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
11848  Rhoa; ras homolog family member A [KO:K04513]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
18479  Pak1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
16706  Ksr1; kinase suppressor of ras 1 [KO:K14958]
12795  Plk3; polo like kinase 3 [KO:K08862] [EC:2.7.11.21]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
56489  Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:2.7.11.10]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
16391  Irf9; interferon regulatory factor 9 [KO:K04693]
20847  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
239114  Il17d; interleukin 17D [KO:K05492]
74256  Cyld; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
12051  Bcl3; B cell leukemia/lymphoma 3 [KO:K09258]
20295  Ccl17; C-C motif chemokine ligand 17 [KO:K21083]
20299  Ccl22; C-C motif chemokine ligand 22 [KO:K21095]
17164  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
56619  Clec4e; C-type lectin domain family 4, member e [KO:K10059]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
17246  Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
16362  Irf1; interferon regulatory factor 1 [KO:K09444]
17474  Clec4d; C-type lectin domain family 4, member d [KO:K10058]
56760  Clec1b; C-type lectin domain family 1, member b [KO:K10070]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C00159  D-Mannose
C00165  Diacylglycerol
C00584  Prostaglandin E2
C00965  1,3-beta-D-Glucan
C01019  L-Fucose
C01245  D-myo-Inositol 1,4,5-trisphosphate
C16844  Hydroxyl radical
C21790  Mycobacterial trehalose dimycolate
C21791  Rhodocytin
G13115  Mannose-capped lipoarabinomannan
Reference
PMID:27291962
  Authors
Geijtenbeek TB, Gringhuis SI
  Title
C-type lectin receptors in the control of T helper cell differentiation.
  Journal
Nat Rev Immunol 16:433-48 (2016)
DOI:10.1038/nri.2016.55
Reference
PMID:21350579
  Authors
Hajishengallis G, Lambris JD
  Title
Microbial manipulation of receptor crosstalk in innate immunity.
  Journal
Nat Rev Immunol 11:187-200 (2011)
DOI:10.1038/nri2918
Reference
PMID:28604735
  Authors
Iliev ID, Leonardi I
  Title
Fungal dysbiosis: immunity and interactions at mucosal barriers.
  Journal
Nat Rev Immunol 17:635-646 (2017)
DOI:10.1038/nri.2017.55
Reference
PMID:25002863
  Authors
Richardson MB, Williams SJ
  Title
MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns.
  Journal
Front Immunol 5:288 (2014)
DOI:10.3389/fimmu.2014.00288
Reference
PMID:21924922
  Authors
Vautier S, MacCallum DM, Brown GD
  Title
C-type lectin receptors and cytokines in fungal immunity.
  Journal
Cytokine 58:89-99 (2012)
DOI:10.1016/j.cyto.2011.08.031
Reference
PMID:22170181
  Authors
Gauglitz GG, Callenberg H, Weindl G, Korting HC
  Title
Host defence against Candida albicans and the role of pattern-recognition receptors.
  Journal
Acta Derm Venereol 92:291-8 (2012)
DOI:10.2340/00015555-1250
Reference
PMID:22973279
  Authors
Cunha C, Carvalho A, Esposito A, Bistoni F, Romani L
  Title
DAMP signaling in fungal infections and diseases.
  Journal
Front Immunol 3:286 (2012)
DOI:10.3389/fimmu.2012.00286
Reference
PMID:29449845
  Authors
Tang J, Lin G, Langdon WY, Tao L, Zhang J
  Title
Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.
  Journal
Front Immunol 9:123 (2018)
DOI:10.3389/fimmu.2018.00123
Reference
PMID:27999992
  Authors
Mayer S, Raulf MK, Lepenies B
  Title
C-type lectins: their network and roles in pathogen recognition and immunity.
  Journal
Histochem Cell Biol 147:223-237 (2017)
DOI:10.1007/s00418-016-1523-7
Reference
PMID:23570314
  Authors
Plato A, Willment JA, Brown GD
  Title
C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways.
  Journal
Int Rev Immunol 32:134-56 (2013)
DOI:10.3109/08830185.2013.777065
Reference
PMID:22344277
  Authors
Dupaul-Chicoine J, Saleh M
  Title
A new path to IL-1beta production controlled by caspase-8.
  Journal
Nat Immunol 13:211-2 (2012)
DOI:10.1038/ni.2241
Reference
PMID:24009832
  Authors
Batbayar S, Lee DH, Kim HW
  Title
Immunomodulation of Fungal beta-Glucan in Host Defense Signaling by Dectin-1.
  Journal
Biomol Ther (Seoul) 20:433-45 (2012)
DOI:10.4062/biomolther.2012.20.5.433
Reference
PMID:28606994
  Authors
Bendickova K, Tidu F, Fric J
  Title
Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.
  Journal
EMBO Mol Med 9:990-999 (2017)
DOI:10.15252/emmm.201707698
Reference
PMID:18998127
  Authors
den Dunnen J, Gringhuis SI, Geijtenbeek TB
  Title
Innate signaling by the C-type lectin DC-SIGN dictates immune responses.
  Journal
Cancer Immunol Immunother 58:1149-57 (2009)
DOI:10.1007/s00262-008-0615-1
Reference
PMID:28640912
  Authors
Marakalala MJ, Ndlovu H
  Title
Signaling C-type lectin receptors in antimycobacterial immunity.
  Journal
PLoS Pathog 13:e1006333 (2017)
DOI:10.1371/journal.ppat.1006333
Reference
PMID:24867235
  Authors
Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW, Geijtenbeek TB
  Title
Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKepsilon- and CYLD-dependent Bcl3 activation.
  Journal
Nat Commun 5:3898 (2014)
DOI:10.1038/ncomms4898
Reference
PMID:19521399
  Authors
Geijtenbeek TB, Gringhuis SI
  Title
Signalling through C-type lectin receptors: shaping immune responses.
  Journal
Nat Rev Immunol 9:465-79 (2009)
DOI:10.1038/nri2569
Reference
PMID:19122653
  Authors
Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, Geijtenbeek TB
  Title
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk.
  Journal
Nat Immunol 10:203-13 (2009)
DOI:10.1038/ni.1692
Related
pathway
mmu04658  Th1 and Th2 cell differentiation
mmu04659  Th17 cell differentiation
KO pathway
ko04625   
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