KEGG   PATHWAY: biu04660
Entry
biu04660                    Pathway                                

Name
T cell receptor signaling pathway - Bos indicus (zebu cattle)
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
biu04660  T cell receptor signaling pathway
biu04660

Other DBs
GO: 0050852
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109569960  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
109569940  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
109569992  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
109577671  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
109558922  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
109566151  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
109566150  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
109570498  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
109572368  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
109563811  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
109565800  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
109574975  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
109578681  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
109562249  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
109560451  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
109560012  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
109566126  NCK2; cytoplasmic protein NCK2 [KO:K19862]
109565687  VAV2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730]
109560955  VAV1; proto-oncogene vav [KO:K05730]
109556793  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
109559835  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
109574040  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
109554525  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
109555415  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
109567943  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
109564925  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
109576171  RHOA; transforming protein RhoA [KO:K04513]
109574100  CDC42; cell division control protein 42 homolog [KO:K04393]
109562672  DLG1; disks large homolog 1 [KO:K12076]
109577010  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109577419  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
109567698  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
109563107  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109553732  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109560300  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109566227  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
109563306  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
109577750  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
109567554  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
109572084  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
109566002  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109564346  SOS2; son of sevenless homolog 2 [KO:K03099]
109564913  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109570973  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109565363  FOS; proto-oncogene c-Fos [KO:K04379]
109556235  JUN; transcription factor AP-1 [KO:K04448]
109567889  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
109578732  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
109556122  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
109577685  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
109563902  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
109560948  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
109561331  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109560650  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109553773  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109553086  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109553353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
109560296  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
109554392  RELA; transcription factor p65 [KO:K04735]
109575581  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109572576  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
109577350  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
109569809  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
109569829  ICOS; inducible T-cell costimulator [KO:K06713]
109555532  CD40LG; CD40 ligand [KO:K03161]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109578066  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109568007  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
109574056  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
109556613  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
109569818  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
109558908  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
109568926  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
109571028  IL2; interleukin-2 [KO:K05429]
109561213  IL4; interleukin-4 [KO:K05430]
109561216  IL5; interleukin-5 [KO:K05428]
109570808  IL10; interleukin-10 [KO:K05443]
109558719  IFNG; interferon gamma [KO:K04687]
109561218  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
109577428  TNF; tumor necrosis factor [KO:K03156]
109559308  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
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
biu04064  NF-kappa B signaling pathway
biu04120  Ubiquitin mediated proteolysis
biu04151  PI3K-Akt signaling pathway
biu04514  Cell adhesion molecules
biu04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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