KEGG   PATHWAY: pvp04660
Entry
pvp04660                    Pathway                                
Name
T cell receptor signaling pathway - Pteropus vampyrus (large 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
pvp04660  T cell receptor signaling pathway
pvp04660

Other DBs
GO: 0050852
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288460  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
105288499  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
105288616  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
105288780  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
105288852  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105288933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105289077  BCL10; B-cell lymphoma/leukemia 10 isoform X2 [KO:K07368]
105289236  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289628  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
105289957  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
105290433  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
105290574  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
105292175  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
105292759  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293031  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293539  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
105293547  IL5; interleukin-5 [KO:K05428]
105293550  IL4; interleukin-4 [KO:K05430]
105293570  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
105293794  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294602  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
105295010  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105295260  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
105295648  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105295781  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
105295941  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
105295953  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
105296040  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
105296266  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296533  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296931  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
105297002  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
105297060  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
105297140  [KO:K02649]
105297614  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
105297866  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105297999  RELA; transcription factor p65 [KO:K04735]
105298067  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
105298133  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
105298317  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
105298420  ICOS; inducible T-cell costimulator [KO:K06713]
105298421  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
105298423  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298743  [KO:K19862]
105298753  NCK2; cytoplasmic protein NCK2 [KO:K19862]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299213  FOS; proto-oncogene c-Fos [KO:K04379]
105299291  PPP2R5C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
105299314  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299451  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
105299964  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105299978  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105300159  [KO:K04456] [EC:2.7.11.1]
105300174  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
105300180  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
105300821  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
105300826  NCK1; cytoplasmic protein NCK1 [KO:K07365]
105301022  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301110  VAV1; proto-oncogene vav [KO:K05730]
105301262  IFNG; interferon gamma [KO:K04687]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301511  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
105301596  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
105302208  IL2; interleukin-2 [KO:K05429]
105302299  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
105302300  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
105302383  RHOA; transforming protein RhoA [KO:K04513]
105302532  IKBKG; NF-kappa-B essential modulator [KO:K07210]
105302942  [KO:K05730]
105302966  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
105303020  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
105303144  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105303182  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105303199  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105303461  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304489  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304587  LAT; linker for activation of T-cells family member 1 [KO:K07362]
105304619  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105305325  TNF; tumor necrosis factor [KO:K03156]
105305747  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306273  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
105306596  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105306810  [KO:K07360] [EC:2.7.10.2]
105307045  CD40LG; CD40 ligand [KO:K03161]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307393  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307700  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
105308212  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
105308283  [KO:K04441] [EC:2.7.11.24]
105308612  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
105308675  [KO:K18052] [EC:2.7.11.13]
105308926  IL10; interleukin-10 [KO:K05443]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309263  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309591  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X2 [KO:K11583]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105309828  [KO:K07293] [EC:3.1.3.48]
105309876  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
105310172  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
105310192  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
105310193  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
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
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04064  NF-kappa B signaling pathway
pvp04120  Ubiquitin mediated proteolysis
pvp04151  PI3K-Akt signaling pathway
pvp04514  Cell adhesion molecule (CAM) interaction
pvp04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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