KEGG   PATHWAY: bbub04660
Entry
bbub04660                   Pathway                                
Name
T cell receptor signaling pathway - Bubalus bubalis (water buffalo)
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
bbub04660  T cell receptor signaling pathway
bbub04660

Other DBs
GO: 0050852
Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102388922  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
102388997  [KO:K10784]
102389208  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102389987  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X4 [KO:K06478] [EC:3.1.3.48]
102390133  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
102390146  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102390438  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102390460  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
102390574  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X3 [KO:K05697] [EC:3.1.3.48]
102390645  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
102390741  LCP2; lymphocyte cytosolic protein 2 isoform X5 [KO:K07361]
102391021  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
102391225  PAK3; serine/threonine-protein kinase PAK 3 isoform X4 [KO:K05733] [EC:2.7.11.1]
102392054  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
102392112  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102392164  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
102392913  SOS1; son of sevenless homolog 1 isoform X3 [KO:K03099]
102392995  KRAS; GTPase KRas isoform X2 [KO:K07827]
102393434  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
102393791  FOS; proto-oncogene C-Fos [KO:K04379]
102393986  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X6 [KO:K04354]
102394706  IKBKG; NF-kappa-B essential modulator isoform X6 [KO:K07210]
102394713  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102395384  [KO:K02649]
102395421  IL2; interleukin-2 precursor [KO:K05429]
102396206  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102396397  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102396554  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
102396572  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
102396612  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X5 [KO:K17332]
102396842  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102396861  DLG1; disks large homolog 1 isoform X6 [KO:K12076]
102397066  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
102397131  IL4; interleukin-4 precursor [KO:K05430]
102397149  MAPK14; mitogen-activated protein kinase 14 isoform X4 [KO:K04441] [EC:2.7.11.24]
102397161  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X7 [KO:K07369] [EC:3.4.22.-]
102397528  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
102397694  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102397755  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102397938  RELA; transcription factor P65 [KO:K04735]
102397969  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102398309  IL5; interleukin-5 precursor [KO:K05428]
102398465  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102398540  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X2 [KO:K11584]
102398646  CD40LG; CD40 ligand [KO:K03161]
102398761  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102398886  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102399159  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
102399287  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102399487  NRAS; GTPase NRas isoform X2 [KO:K07828]
102399525  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102399613  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
102400064  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102400354  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
102400472  [KO:K04354]
102400519  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102400522  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
102400790  IL10; interleukin-10 precursor [KO:K05443]
102400804  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102401069  CTLA4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
102401080  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
102401129  [KO:K07293] [EC:3.1.3.48]
102401744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102401798  ICOS; inducible T-cell costimulator isoform X1 [KO:K06713]
102402025  RHOA; transforming protein RhoA [KO:K04513]
102402670  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102403192  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
102403296  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102403335  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
102403452  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
102403472  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102403930  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
102404165  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102404517  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102404610  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102404881  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
102404912  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
102405224  JUN; transcription factor AP-1 [KO:K04448]
102405817  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
102406385  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102406434  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102406784  LCK; tyrosine-protein kinase Lck isoform X3 [KO:K05856] [EC:2.7.10.2]
102407178  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102407346  VAV2; guanine nucleotide exchange factor VAV2 isoform X4 [KO:K05730]
102407460  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102408544  [KO:K07360] [EC:2.7.10.2]
102409320  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
102409373  CARD11; caspase recruitment domain-containing protein 11 isoform X2 [KO:K07367]
102409598  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
102409665  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102409928  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
102409945  NCK2; cytoplasmic protein NCK2 [KO:K19862]
102410169  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102411485  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
102411610  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X22 [KO:K11584]
102412230  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
102412333  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
102412395  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102412546  [KO:K03456]
102412626  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102412787  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102412823  SOS2; son of sevenless homolog 2 [KO:K03099]
102412869  [KO:K03456]
102412922  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102413480  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446]
102413568  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
102413723  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
102414330  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
102414520  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
102414534  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
102414603  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
102414972  NCK1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
102415109  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102415113  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X4 [KO:K04427] [EC:2.7.11.25]
102415287  VAV1; proto-oncogene vav [KO:K05730]
102415631  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102416287  FYN; tyrosine-protein kinase Fyn isoform X3 [KO:K05703] [EC:2.7.10.2]
102416494  IFNG; interferon gamma precursor [KO:K04687]
102416502  LAT; linker for activation of T-cells family member 1 isoform X3 [KO:K07362]
102416629  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
112587129  [KO:K02833]
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
bbub04010  MAPK signaling pathway
bbub04020  Calcium signaling pathway
bbub04064  NF-kappa B signaling pathway
bbub04120  Ubiquitin mediated proteolysis
bbub04151  PI3K-Akt signaling pathway
bbub04514  Cell adhesion molecules
bbub04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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