KEGG   PATHWAY: bta04660
Entry
bta04660                    Pathway                                
Name
T cell receptor signaling pathway - Bos taurus (cow)
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
bta04660  T cell receptor signaling pathway
bta04660

Other DBs
GO: 0050852
Organism
Bos taurus (cow) [GN:bta]
Gene
100300850  T cell receptor alpha variable 18 [KO:K10784]
509513  uncharacterized LOC509513 precursor [KO:K10785]
100300510  T cell receptor beta constant 1 [KO:K10785]
281053  CD3D; T-cell surface glycoprotein CD3 delta chain precursor [KO:K06450]
281054  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
281055  CD3G; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452]
281056  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
407098  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
281060  CD8A; T-cell surface glycoprotein CD8 alpha chain precursor [KO:K06458]
508633  CD8B; T-cell surface glycoprotein CD8 beta chain precursor [KO:K06459]
407152  PTPRC; receptor-type tyrosine-protein phosphatase C precursor [KO:K06478] [EC:3.1.3.48]
508890  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
527263  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
504509  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
513244  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
514735  LAT; linker for activation of T-cells family member 1 precursor [KO:K07362]
522311  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
504733  TEC; tyrosine-protein kinase Tec isoform X3 [KO:K07364] [EC:2.7.10.2]
536154  NCK1; cytoplasmic protein NCK1 [KO:K07365]
526430  NCK2; cytoplasmic protein NCK2 [KO:K19862]
521961  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
617345  VAV1; proto-oncogene vav [KO:K05730]
515718  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
522346  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
535298  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
533729  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
513673  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
534526  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
539742  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
513432  PAK5; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
539224  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
338049  RHOA; transforming protein RhoA [KO:K04513]
532712  CDC42; cell division control protein 42 homolog [KO:K04393]
785291  DLG1; disks large homolog 1 isoform X3 [KO:K12076]
534492  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
535327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
512943  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
618906  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
281987  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
286852  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
533527  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
790867  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
282321  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
617585  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
511224  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
530401  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
541127  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
537682  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100138040  SOS2; son of sevenless homolog 2 [KO:K03099]
533125  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
100298939  HRAS; GTPase HRas isoform 1 [KO:K02833]
100847184  GTPase HRas-like [KO:K02833]
541140  KRAS; GTPase KRas [KO:K07827]
506322  NRAS; GTPase NRas [KO:K07828]
521196  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
533199  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101905399  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
510434  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
280795  FOS; protein c-Fos [KO:K04379]
280831  JUN; transcription factor Jun [KO:K04448]
505901  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
515377  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
540824  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
504994  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
529146  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
787278  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
539941  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
534125  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
537631  MAPK10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
281073  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
281854  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
281855  IKBKG; NF-kappa-B essential modulator [KO:K07210]
616115  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
508233  RELA; transcription factor p65 [KO:K04735]
282291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
525408  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
506727  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
281050  CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
507026  ICOS; inducible T-cell costimulator precursor [KO:K06713]
282387  CD40LG; CD40 ligand [KO:K03161]
112445051  CD40 ligand [KO:K03161]
282308  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
286865  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
282307  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
282306  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
517948  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
504531  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100138102  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
534923  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
280991  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100137872  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
535622  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
508367  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
790875  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
613842  PDCD1; programmed cell death protein 1 precursor [KO:K06744]
281732  CTLA4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
512312  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
533590  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X3 [KO:K07293] [EC:3.1.3.48]
526769  tyrosine-protein phosphatase non-receptor type 11 isoform X8 [KO:K07293] [EC:3.1.3.48]
282320  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
524361  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
616695  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
535321  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100138150  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]
132344360  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
508045  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
509290  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
782110  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
533147  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
100298789  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
787607  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X3 [KO:K11583]
132342097  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
505915  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
505757  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
533617  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
533788  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
100134966  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
525906  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
280822  IL2; interleukin-2 precursor [KO:K05429]
280824  IL4; interleukin-4 precursor [KO:K05430]
280825  IL5; interleukin-5 precursor [KO:K05428]
281246  IL10; interleukin-10 precursor [KO:K05443]
281237  IFNG; interferon gamma precursor [KO:K04687]
281095  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
280943  TNF; tumor necrosis factor [KO:K03156]
510618  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
  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
bta04010  MAPK signaling pathway
bta04020  Calcium signaling pathway
bta04064  NF-kappa B signaling pathway
bta04120  Ubiquitin mediated proteolysis
bta04151  PI3K-Akt signaling pathway
bta04514  Cell adhesion molecules
bta04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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