KEGG   PATHWAY: hhv04660
Entry
hhv04660                    Pathway                                
Name
T cell receptor signaling pathway - Hyaena hyaena (striped hyena)
Description
Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells.
Class
Organismal Systems; Immune system
Pathway map
hhv04660  T cell receptor signaling pathway
hhv04660

Other DBs
GO: 0050852
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120229959  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
120229941  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
120229957  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
120238260  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
120220463  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
120245556  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X1 [KO:K06458]
120245545  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
120220011  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
120232408  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
120245246  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
120232052  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
120234079  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
120242177  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
120243339  ITK; tyrosine-protein kinase ITK/TSK isoform X1 [KO:K07363] [EC:2.7.10.2]
120237687  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
120224471  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
120221195  NCK2; cytoplasmic protein NCK2 [KO:K19862]
120226858  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
120247171  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
120247312  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
120235349  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
120228194  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
120229608  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
120244384  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
120241977  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
120242769  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
120226240  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
120232303  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
120229394  RHOA; transforming protein RhoA [KO:K04513]
120249159  transforming protein RhoA-like [KO:K04513]
120233626  cell division control protein 42 homolog [KO:K04393]
120231260  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
120244365  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
120233796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120233829  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120234701  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120235253  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
120228585  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
120225617  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
120233735  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120239494  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120220964  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120236651  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120240942  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
120230427  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
120223543  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
120220282  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
120244628  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
120224815  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
120223392  HRAS; GTPase HRas isoform X1 [KO:K02833]
120223531  KRAS; GTPase KRas [KO:K07827]
120243068  NRAS; GTPase NRas [KO:K07828]
120231327  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120221655  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120242086  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
120238830  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120242212  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
120231952  FOS; proto-oncogene c-Fos [KO:K04379]
120236252  JUN; transcription factor AP-1 [KO:K04448]
120237192  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
120227987  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
120241653  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
120230763  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
120231881  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
120244848  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
120244180  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120232781  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120245677  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
120243217  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
120233999  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
120226622  IKBKG; NF-kappa-B essential modulator [KO:K07210]
120222817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
120240185  RELA; transcription factor p65 [KO:K04735]
120248609  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
120244615  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
120231261  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
120226157  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
120220587  ICOS; inducible T-cell costimulator [KO:K06713]
120220140  CD40LG; CD40 ligand [KO:K03161]
120219997  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120239233  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120247089  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
120233608  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120220979  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
120246696  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120241500  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
120235277  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120244696  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120247774  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120221616  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
120222278  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
120242922  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120229556  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
120220586  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
120220450  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
120236974  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
120242567  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
120238508  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120223033  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120229915  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120222367  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120244090  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
120221673  uncharacterized protein LOC120221673 [KO:K04354]
120231861  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
120245371  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
120248361  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
120240557  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
120248228  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
120248601  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
120238408  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120240155  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120230498  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120231211  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
120244579  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120239104  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
120238026  IL2; interleukin-2 [KO:K05429]
120223325  IL4; interleukin-4 [KO:K05430]
120245481  IL5; interleukin-5 [KO:K05428]
120245581  IL10; interleukin-10 [KO:K05443]
120240808  IFNG; interferon gamma [KO:K04687]
120245487  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
120221913  TNF; tumor necrosis factor [KO:K03156]
120248012  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15122199
  Authors
Chen L.
  Title
Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity.
  Journal
Nat Rev Immunol 4:336-47 (2004)
DOI:10.1038/nri1349
Reference
PMID:15928679
  Authors
Macian F.
  Title
NFAT proteins: key regulators of T-cell development and function.
  Journal
Nat Rev Immunol 5:472-84 (2005)
DOI:10.1038/nri1632
Reference
PMID:15771581
  Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
  Title
Tec family kinases in T lymphocyte development and function.
  Journal
Annu Rev Immunol 23:549-600 (2005)
DOI:10.1146/annurev.immunol.22.012703.104743
Reference
PMID:15084594
  Authors
Huang Y, Wange RL.
  Title
T cell receptor signaling: beyond complex complexes.
  Journal
J Biol Chem 279:28827-30 (2004)
DOI:10.1074/jbc.R400012200
Reference
PMID:14656980
  Authors
Schmitz ML, Bacher S, Dienz O.
  Title
NF-kappaB activation pathways induced by T cell costimulation.
  Journal
FASEB J 17:2187-93 (2003)
DOI:10.1096/fj.02-1100rev
Reference
PMID:11905831
  Authors
Alegre ML, Frauwirth KA, Thompson CB.
  Title
T-cell regulation by CD28 and CTLA-4.
  Journal
Nat Rev Immunol 1:220-8 (2001)
DOI:10.1038/35105024
Reference
PMID:15286727
  Authors
Horejsi V, Zhang W, Schraven B.
  Title
Transmembrane adaptor proteins: organizers of immunoreceptor signalling.
  Journal
Nat Rev Immunol 4:603-16 (2004)
DOI:10.1038/nri1414
Reference
PMID:15343367
  Authors
Baniyash M.
  Title
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response.
  Journal
Nat Rev Immunol 4:675-87 (2004)
DOI:10.1038/nri1434
Reference
PMID:15099566
  Authors
Sechi AS, Wehland J.
  Title
Interplay between TCR signalling and actin cytoskeleton dynamics.
  Journal
Trends Immunol 25:257-65 (2004)
DOI:10.1016/j.it.2004.03.003
Reference
PMID:12669022
  Authors
Okkenhaug K, Vanhaesebroeck B.
  Title
PI3K in lymphocyte development, differentiation and activation.
  Journal
Nat Rev Immunol 3:317-30 (2003)
DOI:10.1038/nri1056
Reference
PMID:15489916
  Authors
Palacios EH, Weiss A.
  Title
Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
  Journal
Oncogene 23:7990-8000 (2004)
DOI:10.1038/sj.onc.1208074
Reference
PMID:12133805
  Authors
Kane LP, Lin J, Weiss A.
  Title
It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation.
  Journal
Trends Immunol 23:413-20 (2002)
DOI:10.1016/S1471-4906(02)02264-0
Reference
PMID:14647476
  Authors
Acuto O, Michel F.
  Title
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
  Journal
Nat Rev Immunol 3:939-51 (2003)
DOI:10.1038/nri1248
Reference
PMID:15308211
  Authors
Finkelstein LD, Schwartzberg PL.
  Title
Tec kinases: shaping T-cell activation through actin.
  Journal
Trends Cell Biol 14:443-51 (2004)
DOI:10.1016/j.tcb.2003.07.001
Reference
PMID:15345216
  Authors
Duan L, Reddi AL, Ghosh A, Dimri M, Band H.
  Title
The Cbl family and other ubiquitin ligases: destructive forces in control of antigen receptor signaling.
  Journal
Immunity 21:7-17 (2004)
DOI:10.1016/j.immuni.2004.06.012
Reference
PMID:14617194
  Authors
Schrum AG, Turka LA, Palmer E.
  Title
Surface T-cell antigen receptor expression and availability for long-term antigenic signaling.
  Journal
Immunol Rev 196:7-24 (2003)
DOI:10.1046/j.1600-065X.2003.00083.x
Reference
PMID:19132916
  Authors
Smith-Garvin JE, Koretzky GA, Jordan MS
  Title
T cell activation.
  Journal
Annu Rev Immunol 27:591-619 (2009)
DOI:10.1146/annurev.immunol.021908.132706
Reference
PMID:12195013
  Authors
Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, Crabtree GR, Brown PO
  Title
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
  Journal
Proc Natl Acad Sci U S A 99:11796-801 (2002)
DOI:10.1073/pnas.092284399
Reference
PMID:19290929
  Authors
Blonska M, Lin X
  Title
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.
  Journal
Immunol Rev 228:199-211 (2009)
DOI:10.1111/j.1600-065X.2008.00749.x
Reference
PMID:17395537
  Authors
Rebeaud F, Hailfinger S, Thome M
  Title
Dlgh1 and Carma1 MAGUK proteins contribute to signal specificity downstream of TCR activation.
  Journal
Trends Immunol 28:196-200 (2007)
DOI:10.1016/j.it.2007.03.004
Reference
PMID:16799472
  Authors
Ashwell JD
  Title
The many paths to p38 mitogen-activated protein kinase activation in the immune system.
  Journal
Nat Rev Immunol 6:532-40 (2006)
DOI:10.1038/nri1865
Reference
PMID:17187070
  Authors
Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC
  Title
Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors.
  Journal
Nat Immunol 8:154-61 (2007)
DOI:10.1038/ni1422
Related
pathway
hhv04010  MAPK signaling pathway
hhv04020  Calcium signaling pathway
hhv04064  NF-kappa B signaling pathway
hhv04120  Ubiquitin mediated proteolysis
hhv04151  PI3K-Akt signaling pathway
hhv04514  Cell adhesion molecules
hhv04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
LinkDB

DBGET integrated database retrieval system