KEGG   PATHWAY: uah04625
uah04625                    Pathway                                

C-type lectin receptor signaling pathway - Ursus arctos horribilis
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
uah04625  C-type lectin receptor signaling pathway

Ursus arctos horribilis [GN:uah]
113257901  CLEC7A; C-type lectin domain family 7 member A isoform X1 [KO:K10074]
113243955  LSP1; lymphocyte-specific protein 1 isoform X1 [KO:K14957]
113257418  GTPase HRas-like [KO:K02833]
113257792  KRAS; GTPase KRas isoform X1 [KO:K07827]
113244394  NRAS; GTPase NRas [KO:K07828]
113253984  MRAS; ras-related protein M-Ras isoform X1 [KO:K07831]
113243291  RRAS; ras-related protein R-Ras isoform X1 [KO:K07829]
113246246  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
113257190  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
113244102  RELA; transcription factor p65 [KO:K04735]
113243449  RELB; transcription factor RelB isoform X1 [KO:K09253]
113254130  IL12A; interleukin-12 subunit alpha [KO:K05406]
113263879  IL12B; interleukin-12 subunit beta [KO:K05425]
113242506  IL1B; interleukin-1 beta [KO:K04519]
113270132  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:]
113266983  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:]
113270688  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:]
113265323  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:]
113251823  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
113251868  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
113252535  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:]
113257114  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
113257782  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
113243814  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
113245972  CALM2; calmodulin-2 [KO:K02183]
113267365  CALM1; calmodulin-1 [KO:K02183]
113241090  calmodulin-like [KO:K02183]
113241128  calmodulin-like protein 3 [KO:K02183]
113243394  CALM3; calmodulin-3 [KO:K02183]
113240902  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
113270682  CALML6; calmodulin-like protein 6 [KO:K02183]
113256068  calmodulin-like [KO:K02183]
113244529  PVALEF; parvalbumin-like EF-hand-containing protein isoform X1 [KO:K02183]
113270001  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:]
113259177  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:]
113263105  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:]
113244743  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
113260378  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
113253544  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
113258729  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
113252399  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
113246078  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
113255635  IL2; interleukin-2 [KO:K05429]
113242596  IL10; interleukin-10 [KO:K05443]
113259091  EGR2; E3 SUMO-protein ligase EGR2 isoform X1 [KO:K12496]
113269992  EGR3; early growth response protein 3 [KO:K12497]
113262761  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:]
113256975  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:]
113267646  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:]
113247020  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
113247462  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
113267721  apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
113248575  caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
113248628  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
113254469  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
113253458  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
113250592  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:]
113247832  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
113245546  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:]
113266131  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
113263101  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113243711  TNF; tumor necrosis factor [KO:K03156]
113261280  IL6; interleukin-6 [KO:K05405]
113256421  IL23A; interleukin-23 subunit alpha [KO:K05426]
113241613  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
113241615  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
113243852  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
113243854  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
113263180  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
113261548  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
113243106  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
113254611  JUN; transcription factor AP-1 [KO:K04448]
113250824  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:]
113258092  C-type lectin domain family 6 member A-like [KO:K17514]
113246719  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
113242920  CD209; CD209 antigen isoform X1 [KO:K06563]
113259947  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
113256876  RHOA; transforming protein RhoA [KO:K04513]
113269353  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:]
113269016  KSR1; kinase suppressor of Ras 1 isoform X1 [KO:K14958]
113254757  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:]
113258578  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
113242466  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:]
113250654  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
113245987  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
113256419  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
113251173  IL17D; interleukin-17D [KO:K05492]
113252226  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:]
113243458  BCL3; B-cell lymphoma 3 protein [KO:K09258]
113251703  CCL17; C-C motif chemokine 17 [KO:K21083]
113252282  CCL22; C-C motif chemokine 22 isoform X1 [KO:K21095]
113242594  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:]
113257936  C-type lectin domain family 4 member E-like isoform X1 [KO:K10059]
113254799  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
113270537  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
113253989  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
113256705  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113254730  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
113255266  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113267192  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
113243572  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
113262966  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
113256295  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
113261712  IRF1; interferon regulatory factor 1 [KO:K09444]
113257934  C-type lectin domain family 4 member D-like isoform X1 [KO:K10058]
113257904  CLEC1B; C-type lectin domain family 1 member B isoform X1 [KO:K10070]
C00027  Hydrogen peroxide
C00076  Calcium cation
C00159  D-Mannose
C00165  Diacylglycerol
C00584  Prostaglandin E2
C00965  1,3-beta-D-Glucan
C01019  6-Deoxy-L-galactose
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)
uah04658  Th1 and Th2 cell differentiation
uah04659  Th17 cell differentiation
KO pathway

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