KEGG   PATHWAY: oro04660
Entry
oro04660                    Pathway                                
Name
T cell receptor signaling pathway - Odobenus rosmarus divergens (Pacific walrus)
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
oro04660  T cell receptor signaling pathway
oro04660

Other DBs
GO: 0050852
Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:oro]
Gene
101362094  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101362244  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101362290  NCK1; cytoplasmic protein NCK1 [KO:K07365]
101362330  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101362594  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
101362885  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
101363063  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101363093  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X1 [KO:K06458]
101363246  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101363525  NRAS; GTPase NRas [KO:K07828]
101363583  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
101363739  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
101363831  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101363847  DLG1; disks large homolog 1 isoform X2 [KO:K12076]
101363849  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
101364103  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101364638  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101365120  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101365373  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101365642  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
101365718  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101366316  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
101366633  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
101366773  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101366888  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
101367134  [KO:K02833]
101367482  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101367488  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101367527  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
101367940  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101368207  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
101368209  TNF; tumor necrosis factor [KO:K03156]
101368461  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
101368625  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
101368686  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101369067  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101369267  PDCD1; programmed cell death protein 1 [KO:K06744]
101369947  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101370100  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101370279  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
101370458  KRAS; GTPase KRas isoform X2 [KO:K07827]
101370689  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101370768  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X2 [KO:K11584]
101371488  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101371535  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
101371800  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101372053  [KO:K07364] [EC:2.7.10.2]
101372149  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101372513  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
101372573  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101372786  HRAS; GTPase HRas isoform X1 [KO:K02833]
101373170  ICOS; inducible T-cell costimulator [KO:K06713]
101373249  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
101373461  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
101374044  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
101374143  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
101374233  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
101374328  [KO:K07293] [EC:3.1.3.48]
101374757  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101374787  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101374850  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
101374874  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
101375346  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101375416  NCK2; cytoplasmic protein NCK2 [KO:K19862]
101376134  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
101376185  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101376533  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101376586  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101376824  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101377143  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101377393  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
101377430  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101377743  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101378289  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
101378353  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
101378358  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
101378378  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101378544  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
101378978  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101379396  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101379699  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
101379900  IL10; interleukin-10 [KO:K05443]
101380728  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101381225  RELA; transcription factor p65 [KO:K04735]
101381252  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
101382078  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101382084  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
101382125  IFNG; interferon gamma [KO:K04687]
101382213  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101382259  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101382270  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101382320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101382558  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101382563  CD40LG; CD40 ligand isoform X1 [KO:K03161]
101382896  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
101383028  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
101383166  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101383262  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
101383468  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
101383637  VAV1; proto-oncogene vav isoform X2 [KO:K05730]
101383652  LAT; linker for activation of T-cells family member 1 [KO:K07362]
101383696  IL5; interleukin-5 [KO:K05428]
101383697  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
101384125  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
101384149  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101384443  IL4; interleukin-4 [KO:K05430]
101384959  IKBKG; NF-kappa-B essential modulator isoform X2 [KO:K07210]
101385000  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101385114  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101385184  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
101385241  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101385267  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101385449  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
101385466  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
101385495  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
101385667  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
101385969  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
101386196  IL2; interleukin-2 [KO:K05429]
101386250  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
101386261  CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
101386271  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
101386560  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
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
oro04010  MAPK signaling pathway
oro04020  Calcium signaling pathway
oro04064  NF-kappa B signaling pathway
oro04120  Ubiquitin mediated proteolysis
oro04151  PI3K-Akt signaling pathway
oro04514  Cell adhesion molecules
oro04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

DBGET integrated database retrieval system