KEGG   PATHWAY: rno04625
Entry
rno04625                    Pathway                                
Name
C-type lectin receptor signaling pathway - Rattus norvegicus (rat)
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
rno04625  C-type lectin receptor signaling pathway
rno04625

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
502902  Clec7a; C-type lectin domain family 7 member A [KO:K10074]
361680  Lsp1; lymphocyte-specific protein 1 [KO:K14957]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
25482  Mras; ras-related protein M-Ras [KO:K07831]
361568  Rras; ras-related protein R-Ras [KO:K07829]
365355  Rras2; ras-related protein R-Ras2 [KO:K07830]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
309165  Rela; transcription factor p65 [KO:K04735]
100360982  Relb; RELB proto-oncogene, NF-kB subunit [KO:K09253]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
24494  Il1b; interleukin-1 beta [KO:K04519]
25155  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
25622  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform 2 [KO:K07293] [EC:3.1.3.48]
360640  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
309452  Nfkb2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
100361818  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446]
311658  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
361400  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
305897  Nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
116562  Il2; interleukin-2 precursor [KO:K05429]
25325  Il10; interleukin-10 precursor [KO:K05443]
114090  Egr2; E3 SUMO-protein ligase EGR2 [KO:K12496]
25148  Egr3; early growth response protein 3 [KO:K12497]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
287362  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
282817  Pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
25166  Casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
64171  Card9; caspase recruitment domain-containing protein 9 [KO:K12794]
83477  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
307366  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform 1 [KO:K07369] [EC:3.4.22.-]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
24835  Tnf; tumor necrosis factor [KO:K03156]
24498  Il6; interleukin-6 precursor [KO:K05405]
155140  Il23a; interleukin-23 subunit alpha precursor [KO:K05426]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516  Jun; transcription factor Jun [KO:K04448]
171136  Cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
450222  Clec4b2; C-type lectin domain family 4 member C [KO:K17514]
25441  Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
288375  Cd209a; CD209a molecule [KO:K06563]
288378  Clec4m; CD209b antigen [KO:K06563]
288386  Cd209cl2; CD209 antigen-like protein C [KO:K06563]
304197  Cd209l1; CD209 antigen-like protein E [KO:K06563]
501797  Cd209e; CD209 antigen-like protein E [KO:K06563]
688750  Cd209f; CD209 antigen-like protein 2 [KO:K06563]
688858  Cd209al3; CD209 antigen-like protein E [KO:K06563]
363856  Cd209d; CD209d molecule [KO:K06563]
100363064  Cd209fl1; CD209 antigen-like protein E [KO:K06563]
688951  Cd209c; CD209 antigen-like protein C [KO:K06563]
367072  Arhgef12; rho guanine nucleotide exchange factor 12 [KO:K07532]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
29431  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
108348076  Ksr1; kinase suppressor of Ras 1 [KO:K14958]
58936  Plk3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
312937  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
680611  Bcl3; B-cell lymphoma 3 protein [KO:K09258]
117518  Ccl17; C-C motif chemokine 17 precursor [KO:K21083]
117551  Ccl22; C-C motif chemokine 22 precursor [KO:K21095]
289014  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
450223  Clec4e; C-type lectin domain family 4 member E [KO:K10059]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
314856  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
24508  Irf1; interferon regulatory factor 1 [KO:K09444]
362432  Clec4d; C-type lectin domain family 4 member D [KO:K10058]
500336  Clec1b; C-type lectin domain family 1 member B [KO:K10070]
691799  Il17d; interleukin-17D precursor [KO:K05492]
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
rno04658  Th1 and Th2 cell differentiation
rno04659  Th17 cell differentiation
KO pathway
ko04625   
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