KEGG   PATHWAY: eju04660
Entry
eju04660                    Pathway                                
Name
T cell receptor signaling pathway - Eumetopias jubatus (Steller sea lion)
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
eju04660  T cell receptor signaling pathway
eju04660

Other DBs
GO: 0050852
Organism
Eumetopias jubatus (Steller sea lion) [GN:eju]
Gene
114196799  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
114198407  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
114198925  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
114198928  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
114198992  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
114199036  CDC42; cell division control protein 42 homolog [KO:K04393]
114199341  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
114199922  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
114200239  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
114200618  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
114200845  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
114200996  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
114201201  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
114201320  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114201455  CD40LG; CD40 ligand [KO:K03161]
114201560  HRAS; GTPase HRas isoform X1 [KO:K02833]
114202353  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114202397  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
114202451  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
114203265  [KO:K04456] [EC:2.7.11.1]
114203268  [KO:K04456] [EC:2.7.11.1]
114203804  IKBKG; NF-kappa-B essential modulator [KO:K07210]
114204406  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
114204458  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
114205217  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
114205461  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
114205545  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
114205617  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114205650  NCK1; cytoplasmic protein NCK1 [KO:K07365]
114206044  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
114206298  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
114206518  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114206837  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
114206945  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
114206954  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114206958  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
114207358  FOS; proto-oncogene c-Fos [KO:K04379]
114207692  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114207903  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
114207931  NRAS; GTPase NRas [KO:K07828]
114208234  IL2; interleukin-2 [KO:K05429]
114208468  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
114208569  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
114208802  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
114209409  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
114209514  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
114209547  IL4; interleukin-4 [KO:K05430]
114209600  IL5; interleukin-5 [KO:K05428]
114209679  NCK2; cytoplasmic protein NCK2 [KO:K19862]
114209685  [KO:K07360] [EC:2.7.10.2]
114209890  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
114210731  PDCD1; programmed cell death protein 1 [KO:K06744]
114211298  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
114211331  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
114211373  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
114211431  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
114211897  SOS2; son of sevenless homolog 2 [KO:K03099]
114211992  ITK; tyrosine-protein kinase ITK/TSK isoform X1 [KO:K07363] [EC:2.7.10.2]
114212152  JUN; transcription factor AP-1 [KO:K04448]
114213021  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
114213130  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
114213370  [KO:K07293] [EC:3.1.3.48]
114213552  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
114214123  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114214380  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
114214409  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114214730  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114214991  IFNG; interferon gamma [KO:K04687]
114214999  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114215523  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114215569  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
114215744  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
114215933  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
114215963  ICOS; inducible T-cell costimulator isoform X1 [KO:K06713]
114216016  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
114216301  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
114216393  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
114216565  KRAS; GTPase KRas isoform X1 [KO:K07827]
114217100  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
114217424  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
114217489  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114217682  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
114217693  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
114217798  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
114217931  NFKBIA; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
114218039  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
114218301  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
114218424  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114218476  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
114218686  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
114218910  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114219111  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
114219700  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
114220346  RELA; transcription factor p65 [KO:K04735]
114220366  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
114221027  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
114221055  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
114221353  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
114221473  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
114221842  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
114221910  IL10; interleukin-10 [KO:K05443]
114221987  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
114222054  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
114222242  TNF; tumor necrosis factor [KO:K03156]
114222247  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114222423  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
114222497  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
114222546  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
114223136  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
114223459  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X1 [KO:K06458]
114223474  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
114224308  [KO:K02649]
114224473  [KO:K04393]
114224631  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114224851  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
114224898  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114225106  RHOA; transforming protein RhoA [KO:K04513]
114225505  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
114225923  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
114226263  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
114226331  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114226659  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
eju04010  MAPK signaling pathway
eju04020  Calcium signaling pathway
eju04064  NF-kappa B signaling pathway
eju04120  Ubiquitin mediated proteolysis
eju04151  PI3K-Akt signaling pathway
eju04514  Cell adhesion molecules
eju04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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