KEGG   PATHWAY: gas04660
Entry
gas04660                    Pathway                                
Name
T cell receptor signaling pathway - Gracilinanus agilis (agile gracile opossum)
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
gas04660  T cell receptor signaling pathway
gas04660

Other DBs
GO: 0050852
Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123230857  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123230879  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
123231496  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
123232107  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
123232290  [KO:K07360] [EC:2.7.10.2]
123232293  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
123232498  [KO:K11584]
123232515  [KO:K07828]
123232952  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
123233025  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
123233148  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
123233359  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
123233372  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
123233417  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
123233889  IL4; interleukin-4 [KO:K05430]
123233974  SOS2; son of sevenless homolog 2 [KO:K03099]
123233999  CD247; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
123234527  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
123235580  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
123235614  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
123235704  IL5; interleukin-5 [KO:K05428]
123235754  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123236476  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
123236652  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
123236785  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
123236829  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123236876  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123236954  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
123237139  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
123237207  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
123237416  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
123237465  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123237498  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
123237600  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
123237620  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123237637  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123237685  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
123237748  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
123237804  FOS; proto-oncogene c-Fos [KO:K04379]
123237869  [KO:K04513]
123237916  [KO:K05735] [EC:2.7.11.1]
123237919  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
123238040  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
123238271  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
123238976  [KO:K04393]
123239093  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
123239417  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
123239466  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123239917  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
123240041  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
123240049  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
123240096  CTLA4; cytotoxic T-lymphocyte protein 4 [KO:K06538]
123240288  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123240362  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
123240520  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
123240795  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123241296  [KO:K04393]
123241835  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
123241905  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
123241906  ICOS; inducible T-cell costimulator [KO:K06713]
123242099  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
123242100  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
123242322  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123242326  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
123242334  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
123242376  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123242395  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
123242569  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
123242595  NCK2; cytoplasmic protein NCK2 [KO:K19862]
123242790  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
123242831  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123242998  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123243007  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123243044  [KO:K07293] [EC:3.1.3.48]
123243232  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
123243674  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
123243860  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123244679  [KO:K06276] [EC:2.7.11.1]
123245100  TNF; tumor necrosis factor [KO:K03156]
123245114  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
123245414  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123245455  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
123245523  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123245668  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
123245714  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
123245946  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
123245974  IL10; interleukin-10 [KO:K05443]
123246567  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
123246700  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
123247194  NRAS; GTPase NRas [KO:K07828]
123247425  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123247552  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
123247656  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
123248655  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123248684  KRAS; GTPase KRas isoform X1 [KO:K07827]
123249099  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
123249295  [KO:K04393]
123249350  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
123249464  RHOA; transforming protein RhoA [KO:K04513]
123249681  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
123250035  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
123250072  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
123250180  IFNG; interferon gamma [KO:K04687]
123250526  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
123250672  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
123251011  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123251137  IL2; interleukin-2 [KO:K05429]
123251179  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123251284  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123251290  RELA; transcription factor p65 isoform X1 [KO:K04735]
123251504  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
123251828  [KO:K07827]
123252118  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
123252235  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
123252239  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
123252331  [KO:K05730]
123252332  [KO:K05730]
123252361  [KO:K04382] [EC:3.1.3.16]
123252892  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
123253292  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
123253558  CD40LG; CD40 ligand [KO:K03161]
123253779  IKBKG; NF-kappa-B essential modulator [KO:K07210]
123254439  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
123255125  PDCD1; programmed cell death protein 1 [KO:K06744]
123256513  [KO:K02649]
123256515  [KO:K02649]
123256872  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
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
gas04010  MAPK signaling pathway
gas04020  Calcium signaling pathway
gas04064  NF-kappa B signaling pathway
gas04120  Ubiquitin mediated proteolysis
gas04151  PI3K-Akt signaling pathway
gas04514  Cell adhesion molecule (CAM) interaction
gas04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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