KEGG   PATHWAY: fca04625
fca04625                    Pathway                                
C-type lectin receptor signaling pathway - Felis catus (domestic cat)
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.
Organismal Systems; Immune system
Pathway map
fca04625  C-type lectin receptor signaling pathway

Felis catus (domestic cat) [GN:fca]
101083523  CLEC7A; C-type lectin domain family 7 member A isoform X3 [KO:K10074]
101094133  LSP1; lymphocyte-specific protein 1 isoform X5 [KO:K14957]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
101092784  MRAS; ras-related protein M-Ras isoform X2 [KO:K07831]
101096187  RRAS; ras-related protein R-Ras isoform X1 [KO:K07829]
101094623  RRAS2; ras-related protein R-Ras2 isoform X2 [KO:K07830]
101096047  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:]
101096604  RELA; transcription factor p65 [KO:K04735]
101085762  RELB; LOW QUALITY PROTEIN: transcription factor RelB [KO:K09253]
493741  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
768273  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
768274  IL1B; interleukin-1 beta precursor [KO:K04519]
101087013  SYK; tyrosine-protein kinase SYK isoform X3 [KO:K05855] [EC:]
101085500  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:]
101083468  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
101080578  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
101080675  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X3 [KO:K04958]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101087993  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101081534  CALM2; calmodulin-2 [KO:K02183]
101099307  calmodulin-like protein 3 [KO:K02183]
102902667  calmodulin-like [KO:K02183]
101091063  CALM3; calmodulin-3 isoform X1 [KO:K02183]
101097703  calmodulin-alpha-like [KO:K02183]
101094679  CALM1; calmodulin-1 [KO:K02183]
111556187  calmodulin-like protein 4 [KO:K02183]
101086824  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
101100214  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101097144  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:]
101086926  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:]
101093097  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:]
101097765  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101090344  PPP3R1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
101101259  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446]
101080520  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101083728  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101098235  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334]
751114  IL2; interleukin-2 precursor [KO:K05429]
493683  IL10; interleukin-10 precursor [KO:K05443]
101082520  EGR2; E3 SUMO-protein ligase EGR2 isoform X1 [KO:K12496]
101086390  EGR3; early growth response protein 3 isoform X1 [KO:K12497]
100126581  PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:]
101087716  PRKCD; protein kinase C delta type [KO:K06068] [EC:]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
101087958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
101092579  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
101088449  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101093152  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
101099570  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
101088885  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
100142684  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:]
101090622  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493687  IL6; interleukin-6 precursor [KO:K05405]
654423  IL23A; interleukin-23 subunit alpha [KO:K05426]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
101097261  JUN; transcription factor AP-1 [KO:K04448]
101101498  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:]
105260732  CLEC6A; C-type lectin domain family 6 member A isoform X1 [KO:K17514]
101089236  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
100462978  CD209; CD209 antigen [KO:K06563]
101085657  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101087171  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:]
101092156  KSR1; kinase suppressor of Ras 1 isoform X9 [KO:K14958]
101088599  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:]
101100378  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:]
101086282  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:]
101084561  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101100970  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
101099224  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101093070  IL17D; interleukin-17D [KO:K05492]
101094641  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:]
101096023  BCL3; B-cell lymphoma 3 protein [KO:K09258]
493832  CCL17; C-C motif chemokine 17 precursor [KO:K21083]
101091326  CCL22; C-C motif chemokine 22 [KO:K21095]
101090833  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X1 [KO:K04443] [EC:]
101094859  CLEC4E; C-type lectin domain family 4 member E [KO:K10059]
101094274  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
101091892  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101093286  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
493939  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
101095633  IRF1; interferon regulatory factor 1 [KO:K09444]
101095108  CLEC4D; LOW QUALITY PROTEIN: C-type lectin domain family 4 member D [KO:K10058]
109491361  CLEC1B; C-type lectin domain family 1 member B [KO:K10070]
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  Trehalose dimycolate
C21791  Rhodocytin
G13115  Mannose-capped lipoarabinomannan
Geijtenbeek TB, Gringhuis SI
C-type lectin receptors in the control of T helper cell differentiation.
Nat Rev Immunol 16:433-48 (2016)
Hajishengallis G, Lambris JD
Microbial manipulation of receptor crosstalk in innate immunity.
Nat Rev Immunol 11:187-200 (2011)
Iliev ID, Leonardi I
Fungal dysbiosis: immunity and interactions at mucosal barriers.
Nat Rev Immunol 17:635-646 (2017)
Richardson MB, Williams SJ
MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns.
Front Immunol 5:288 (2014)
Vautier S, MacCallum DM, Brown GD
C-type lectin receptors and cytokines in fungal immunity.
Cytokine 58:89-99 (2012)
Gauglitz GG, Callenberg H, Weindl G, Korting HC
Host defence against Candida albicans and the role of pattern-recognition receptors.
Acta Derm Venereol 92:291-8 (2012)
Cunha C, Carvalho A, Esposito A, Bistoni F, Romani L
DAMP signaling in fungal infections and diseases.
Front Immunol 3:286 (2012)
Tang J, Lin G, Langdon WY, Tao L, Zhang J
Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.
Front Immunol 9:123 (2018)
Mayer S, Raulf MK, Lepenies B
C-type lectins: their network and roles in pathogen recognition and immunity.
Histochem Cell Biol 147:223-237 (2017)
Plato A, Willment JA, Brown GD
C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways.
Int Rev Immunol 32:134-56 (2013)
Dupaul-Chicoine J, Saleh M
A new path to IL-1beta production controlled by caspase-8.
Nat Immunol 13:211-2 (2012)
Batbayar S, Lee DH, Kim HW
Immunomodulation of Fungal beta-Glucan in Host Defense Signaling by Dectin-1.
Biomol Ther (Seoul) 20:433-45 (2012)
Bendickova K, Tidu F, Fric J
Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.
EMBO Mol Med 9:990-999 (2017)
den Dunnen J, Gringhuis SI, Geijtenbeek TB
Innate signaling by the C-type lectin DC-SIGN dictates immune responses.
Cancer Immunol Immunother 58:1149-57 (2009)
Marakalala MJ, Ndlovu H
Signaling C-type lectin receptors in antimycobacterial immunity.
PLoS Pathog 13:e1006333 (2017)
Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW, Geijtenbeek TB
Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKepsilon- and CYLD-dependent Bcl3 activation.
Nat Commun 5:3898 (2014)
Geijtenbeek TB, Gringhuis SI
Signalling through C-type lectin receptors: shaping immune responses.
Nat Rev Immunol 9:465-79 (2009)
Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, Geijtenbeek TB
Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk.
Nat Immunol 10:203-13 (2009)
fca04658  Th1 and Th2 cell differentiation
fca04659  Th17 cell differentiation
KO pathway

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