KEGG   PATHWAY: gvr04660
Entry
gvr04660                    Pathway                                
Name
T cell receptor signaling pathway - Galeopterus variegatus (Sunda flying lemur)
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
gvr04660  T cell receptor signaling pathway
gvr04660

Other DBs
GO: 0050852
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103582444  [KO:K11583]
103582470  [KO:K07360] [EC:2.7.10.2]
103582610  [KO:K04440] [EC:2.7.11.24]
103582933  [KO:K10784]
103584018  [KO:K11584]
103584948  RHOA; transforming protein RhoA [KO:K04513]
103585050  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
103585172  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103585343  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
103585463  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103585627  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103585752  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103586032  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
103586253  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
103586398  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
103586411  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
103586572  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103586784  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103587477  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587478  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587579  [KO:K04354]
103587883  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103588094  [KO:K07293] [EC:3.1.3.48]
103588798  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103589266  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103589329  NRAS; GTPase NRas [KO:K07828]
103589434  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103589615  IL5; interleukin-5 isoform X1 [KO:K05428]
103589624  IL4; interleukin-4 [KO:K05430]
103590058  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
103590279  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103590415  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
103590618  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103591114  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
103591302  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
103591406  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
103591436  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
103591464  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
103591684  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
103591883  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
103592045  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
103592192  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103592268  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
103592269  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
103592270  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
103592383  TNF; tumor necrosis factor [KO:K03156]
103592390  JUN; transcription factor AP-1 [KO:K04448]
103592396  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103592662  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
103592750  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
103593281  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103593545  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103593609  IL2; interleukin-2 [KO:K05429]
103593683  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103594130  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
103594178  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
103594406  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103594793  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
103594915  [KO:K04354]
103594929  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
103595334  RELA; transcription factor p65 [KO:K04735]
103595366  PDCD1; programmed cell death protein 1 [KO:K06744]
103595392  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103595586  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
103595998  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
103596129  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103596376  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
103596384  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103596394  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
103596789  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
103596898  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103597025  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
103597255  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
103597262  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
103597898  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
103598106  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103598210  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103598251  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103598325  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103598404  [KO:K04354]
103598967  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
103598977  [KO:K04393]
103599260  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
103599396  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103599501  KRAS; GTPase KRas [KO:K07827]
103599527  VAV1; proto-oncogene vav [KO:K05730]
103599785  [KO:K07367]
103599911  ICOS; inducible T-cell costimulator [KO:K06713]
103599912  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
103599915  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
103600170  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
103600263  [KO:K04409] [EC:2.7.11.1]
103600324  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103600438  IL10; interleukin-10 [KO:K05443]
103600750  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103601494  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103601545  [KO:K12076]
103601711  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
103601908  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
103603209  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
103603521  [KO:K04440] [EC:2.7.11.24]
103603905  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
103604169  [KO:K11584]
103604227  [KO:K10784]
103604367  IKBKG; NF-kappa-B essential modulator [KO:K07210]
103604418  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
103604521  PPP3R2; calcineurin subunit B type 2 isoform X1 [KO:K06268]
103605353  [KO:K10785]
103605679  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
103605698  [KO:K04456] [EC:2.7.11.1]
103605815  [KO:K04687]
103605891  FOS; proto-oncogene c-Fos [KO:K04379]
103606318  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103606580  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
103606635  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103606724  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103607039  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
103607164  CD40LG; CD40 ligand isoform X1 [KO:K03161]
103607385  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
103607386  CD8A; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
103607428  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607442  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607777  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
103608454  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103609174  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103609732  [KO:K04687]
103610308  [KO:K07360] [EC:2.7.10.2]
103610513  HRAS; GTPase HRas isoform X1 [KO:K02833]
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
gvr04010  MAPK signaling pathway
gvr04020  Calcium signaling pathway
gvr04064  NF-kappa B signaling pathway
gvr04120  Ubiquitin mediated proteolysis
gvr04151  PI3K-Akt signaling pathway
gvr04514  Cell adhesion molecules
gvr04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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