KEGG   PATHWAY: tod04660
Entry
tod04660                    Pathway                                
Name
T cell receptor signaling pathway - Talpa occidentalis (Iberian mole)
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
tod04660  T cell receptor signaling pathway
tod04660

Other DBs
GO: 0050852
Organism
Talpa occidentalis (Iberian mole) [GN:tod]
Gene
119239888  T-cell surface glycoprotein CD3 delta chain [KO:K06450]
119239887  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
119242080  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
119242275  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
119247775  CD4; T-cell surface glycoprotein CD4 isoform X3 [KO:K06454]
119259889  T-cell surface glycoprotein CD8 alpha chain-like [KO:K06458]
119259890  T-cell surface glycoprotein CD8 alpha chain-like isoform X2 [KO:K06458]
119259149  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
119234713  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
119235229  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
119252791  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
119259916  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
119235546  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
119240182  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
119235500  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
119260950  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
119257736  NCK1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
119246043  cytoplasmic protein NCK1-like [KO:K07365]
119259291  NCK2; cytoplasmic protein NCK2 [KO:K19862]
119235099  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
119231223  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
119240642  VAV1; proto-oncogene vav [KO:K05730]
119247238  GRAP2; GRB2-related adapter protein 2 isoform X2 [KO:K07366]
119232938  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
119255656  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
119257420  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
119245962  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
119249295  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
119232641  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
119237906  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
119242628  transforming protein RhoA-like [KO:K04513]
119260155  RHOA; transforming protein RhoA [KO:K04513]
119237218  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
119257413  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
119252387  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
119252388  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
119247132  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
119247133  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
119235450  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
119234581  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119234881  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119243687  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
119231203  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
119259019  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
119242960  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
119236570  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
119248976  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X3 [KO:K17333]
119259378  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
119239071  SOS2; son of sevenless homolog 2 [KO:K03099]
119238466  RASGRP1; RAS guanyl-releasing protein 1 isoform X2 [KO:K04350]
119249824  HRAS; GTPase HRas isoform X1 [KO:K02833]
119247626  KRAS; GTPase KRas isoform X1 [KO:K07827]
119236713  NRAS; GTPase NRas [KO:K07828]
119255730  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119238768  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
119240577  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119234388  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119241775  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119238328  FOS; protein c-Fos [KO:K04379]
119235421  JUN; transcription factor Jun [KO:K04448]
119244662  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
119240158  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
119236412  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
119243010  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
119252700  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
119240438  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
119234816  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119236621  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
119261431  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
119256545  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
119233588  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
119257853  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
119245781  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
119243680  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
119248814  RELA; transcription factor p65 isoform X1 [KO:K04735]
119239019  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
119249286  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
119252518  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
119256129  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
119255179  ICOS; inducible T-cell costimulator [KO:K06713]
119246511  CD40LG; CD40 ligand [KO:K03161]
119237093  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119260810  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119241117  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119257726  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119236721  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
119257304  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119242012  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
119244519  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
119239481  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119249321  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119244638  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
119230450  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
119257489  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
119254910  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
119254827  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
119247764  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
119244965  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
119257786  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
119243468  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119249625  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
119240660  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
119234435  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
119242887  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X4 [KO:K04354]
119260982  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
119257744  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
119239016  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
119246800  PPP2R3B; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
119234468  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
119250005  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
119252478  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
119239170  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
119239382  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
119257555  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
119233628  IL2; interleukin-2 [KO:K05429]
119243728  IL4; interleukin-4 [KO:K05430]
119243489  IL5; interleukin-5 [KO:K05428]
119233943  IL10; interleukin-10 [KO:K05443]
119248294  IFNG; interferon gamma [KO:K04687]
119242737  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
119253235  TNF; tumor necrosis factor isoform X1 [KO:K03156]
119248102  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
tod04010  MAPK signaling pathway
tod04020  Calcium signaling pathway
tod04064  NF-kappa B signaling pathway
tod04120  Ubiquitin mediated proteolysis
tod04151  PI3K-Akt signaling pathway
tod04514  Cell adhesion molecules
tod04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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