KEGG   PATHWAY: pale04660
Entry
pale04660                   Pathway                                
Name
T cell receptor signaling pathway - Pteropus alecto (black 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
pale04660  T cell receptor signaling pathway
pale04660

Other DBs
GO: 0050852
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102898423  T-cell receptor beta-2 chain C region [KO:K10785]
102891942  uncharacterized protein LOC102891942 [KO:K10785]
102894486  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
102894744  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
102894240  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
102896086  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
102883844  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
102884096  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
102898377  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
102891182  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
102896849  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
102883976  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
102891430  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
102883829  LAT; linker for activation of T-cells family member 1 [KO:K07362]
102880728  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
102890023  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
102882952  NCK1; cytoplasmic protein NCK1 [KO:K07365]
102887531  NCK2; cytoplasmic protein NCK2 [KO:K19862]
102883521  VAV1; proto-oncogene vav [KO:K05730]
102886772  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
102884766  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
102895856  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102880323  PAK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102886796  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102886090  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
102880509  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
102884535  PAK5; serine/threonine-protein kinase PAK 5 isoform X2 [KO:K05736] [EC:2.7.11.1]
102896564  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
102891515  RHOA; transforming protein RhoA [KO:K04513]
102889114  CDC42; cell division control protein 42 homolog [KO:K04393]
102887557  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
102895900  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888602  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888845  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102877720  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102896228  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102880029  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102883156  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102898473  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102894471  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102895490  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102880857  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102886274  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102884312  NFATC3; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102877927  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102891428  FOS; proto-oncogene c-Fos [KO:K04379]
102896121  JUN; transcription factor AP-1 [KO:K04448]
102892408  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
102879559  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
102881834  BCL10; B-cell lymphoma/leukemia 10 isoform X2 [KO:K07368]
107195812  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
102882452  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102892533  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102885064  MAPK10; mitogen-activated protein kinase 10 isoform X5 [KO:K04440] [EC:2.7.11.24]
102890689  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102892777  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102879469  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102893261  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102880203  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102880692  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102878395  RELA; transcription factor p65 [KO:K04735]
102891056  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102881802  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102887733  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102884019  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
102884694  ICOS; inducible T-cell costimulator [KO:K06713]
102885468  CD40LG; CD40 ligand [KO:K03161]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102896950  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102896654  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X2 [KO:K04415] [EC:2.7.11.25]
102897751  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102882441  GSK3B; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
102879076  PDCD1; programmed cell death protein 1 [KO:K06744]
102884443  CTLA4; cytotoxic T-lymphocyte protein 4 [KO:K06538]
102895931  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
102889219  PTPN11; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102887205  tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102885289  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102887013  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102894487  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102888699  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102888692  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
102882824  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
102892945  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
102896806  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
102891533  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
102884648  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102879054  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102897902  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
102895399  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
102881266  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102898938  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102890283  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102895516  IL2; interleukin-2 [KO:K05429]
102890025  IL4; interleukin-4 [KO:K05430]
102890771  IL5; interleukin-5 [KO:K05428]
102887289  IL10; interleukin-10 [KO:K05443]
102882436  IFNG; interferon gamma precursor [KO:K04687]
102893042  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102887632  TNF; tumor necrosis factor [KO:K03156]
102894222  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
pale04010  MAPK signaling pathway
pale04020  Calcium signaling pathway
pale04064  NF-kappa B signaling pathway
pale04120  Ubiquitin mediated proteolysis
pale04151  PI3K-Akt signaling pathway
pale04514  Cell adhesion molecules
pale04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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