KEGG   PATHWAY: pgig04660
Entry
pgig04660                   Pathway                                
Name
T cell receptor signaling pathway - Pteropus giganteus (Indian flying fox)
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
pgig04660  T cell receptor signaling pathway
pgig04660

Other DBs
GO: 0050852
Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120589132  uncharacterized protein LOC120589132 [KO:K10785]
120622049  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
120622048  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
120622052  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
120617704  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
120611664  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
120594587  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
120594517  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
120619231  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
120581990  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
120608606  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
120610234  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
120614724  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
120620147  LAT; linker for activation of T-cells family member 1 [KO:K07362]
120613855  ITK; tyrosine-protein kinase ITK/TSK isoform X1 [KO:K07363] [EC:2.7.10.2]
120588037  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
120582120  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
120584471  NCK2; cytoplasmic protein NCK2 [KO:K19862]
120615458  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
120584964  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
120618875  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
120602991  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
120600272  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
120590385  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
120592835  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
120612304  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
120596145  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
120611912  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
120587192  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
120582355  RHOA; transforming protein RhoA [KO:K04513]
120596202  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
120592931  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
120602825  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
120602826  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
120597571  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120597692  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120603668  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
120591098  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120606631  PPP3CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
120609542  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120594548  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120596960  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120583821  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
120603824  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
120593904  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
120604448  SOS2; son of sevenless homolog 2 [KO:K03099]
120621751  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
120587204  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
120584662  HRAS; GTPase HRas isoform X1 [KO:K02833]
120618351  KRAS; GTPase KRas isoform X1 [KO:K07827]
120585069  NRAS; GTPase NRas isoform X1 [KO:K07828]
120621476  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120604492  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
120615382  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
120606851  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120620121  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120619517  FOS; proto-oncogene c-Fos [KO:K04379]
120621837  JUN; transcription factor AP-1 [KO:K04448]
120609009  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
120615709  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
120583290  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
120595002  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
120598851  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
120616614  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
120609636  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120588349  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120609204  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
120595665  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
120605919  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
120591230  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
120584840  RELA; transcription factor p65 [KO:K04735]
120620765  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
120596238  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
120596185  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
120587556  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
120587560  ICOS; inducible T-cell costimulator [KO:K06713]
120612438  CD40LG; CD40 ligand [KO:K03161]
120606549  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120608247  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120620206  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
120582132  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120596984  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120585845  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
120620273  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
120613959  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120595669  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120619079  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120584101  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
120589252  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
120586669  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120601668  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
120587558  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
120611673  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
120614076  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
120606707  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
120581292  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120589049  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120583980  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120621983  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120581501  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
120613401  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
120582867  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
120582112  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
120620761  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
120610948  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
120603778  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120617516  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120596143  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
120619709  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120600686  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120598144  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
120616276  IL2; interleukin-2 [KO:K05429]
120616686  IL4; interleukin-4 [KO:K05430]
120616515  IL5; interleukin-5 [KO:K05428]
120618001  IL10; interleukin-10 isoform X1 [KO:K05443]
120604831  IFNG; interferon gamma [KO:K04687]
120616524  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
120618944  TNF; tumor necrosis factor [KO:K03156]
120604974  CDK4; cyclin-dependent kinase 4 isoform X1 [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
  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
pgig04010  MAPK signaling pathway
pgig04020  Calcium signaling pathway
pgig04064  NF-kappa B signaling pathway
pgig04120  Ubiquitin mediated proteolysis
pgig04151  PI3K-Akt signaling pathway
pgig04514  Cell adhesion molecules
pgig04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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