KEGG   PATHWAY: oas04660
Entry
oas04660                    Pathway                                
Name
T cell receptor signaling pathway - Ovis aries (sheep)
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
oas04660  T cell receptor signaling pathway
oas04660

Other DBs
GO: 0050852
Organism
Ovis aries (sheep) [GN:oas]
Gene
100144756  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100169938  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100194428  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100216439  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
100217411  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100302078  RHOA; transforming protein RhoA [KO:K04513]
100302082  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100307045  NCK1; cytoplasmic protein NCK1 [KO:K07365]
101102015  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X8 [KO:K11584]
101102148  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
101102191  RELA; transcription factor p65 [KO:K04735]
101102438  NRAS; GTPase NRas [KO:K07828]
101102485  TEC; tyrosine-protein kinase Tec isoform X4 [KO:K07364] [EC:2.7.10.2]
101102732  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101102792  CDC42; cell division control protein 42 homolog [KO:K04393]
101102917  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
101103028  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
101103341  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101103464  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
101103712  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
101104699  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
101105277  LCP2; lymphocyte cytosolic protein 2 isoform X2 [KO:K07361]
101105504  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
101106246  [KO:K04513]
101107037  [KO:K07293] [EC:3.1.3.48]
101107332  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
101107354  VAV1; proto-oncogene vav [KO:K05730]
101107589  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
101107792  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
101107882  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
101108056  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X4 [KO:K04427] [EC:2.7.11.25]
101108097  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X6 [KO:K04446]
101108104  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101108228  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
101108352  [KO:K04382] [EC:3.1.3.16]
101108511  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
101108643  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
101109363  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101109519  [KO:K03456]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101109893  GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101110137  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
101110299  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X5 [KO:K04354]
101110391  PAK3; serine/threonine-protein kinase PAK 3 isoform X2 [KO:K05733] [EC:2.7.11.1]
101110725  LAT; linker for activation of T-cells family member 1 isoform X3 [KO:K07362]
101110813  CARD11; caspase recruitment domain-containing protein 11 isoform X3 [KO:K07367]
101110885  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101111143  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101111756  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
101112573  PAK6; serine/threonine-protein kinase PAK 6 isoform X2 [KO:K05735] [EC:2.7.11.1]
101112639  [KO:K07360] [EC:2.7.10.2]
101112899  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
101113372  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
101113409  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X6 [KO:K04354]
101113426  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
101113567  ICOS; inducible T-cell costimulator isoform X1 [KO:K06713]
101113618  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101114233  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X2 [KO:K11583]
101114255  NCK2; cytoplasmic protein NCK2 [KO:K19862]
101114308  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X3 [KO:K07293] [EC:3.1.3.48]
101114404  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101114438  [KO:K10785]
101114930  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101115152  PAK4; serine/threonine-protein kinase PAK 4 isoform X2 [KO:K05734] [EC:2.7.11.1]
101115302  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101115429  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101115485  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
101115956  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101116201  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101116223  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
101116274  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
101116812  [KO:K11583]
101117094  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X2 [KO:K04415] [EC:2.7.11.25]
101117211  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
101117264  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101117607  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X3 [KO:K17333]
101118312  NFKBIE; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101118799  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
101118865  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
101119239  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101119424  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
101120665  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
101120709  VAV3; guanine nucleotide exchange factor VAV3 isoform X5 [KO:K05730]
101120802  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101120826  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101121636  PDCD1; programmed cell death protein 1 isoform X3 [KO:K06744]
101122602  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
101122781  IL4; interleukin-4 precursor [KO:K05430]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101123517  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114108599  [KO:K04393]
114108765  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114110058  [KO:K04364]
114111443  [KO:K03456]
114114919  [KO:K02833]
114116812  [KO:K04513]
114118284  [KO:K04427] [EC:2.7.11.25]
443009  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
443040  CTLA4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
443218  FOS; protein c-Fos [KO:K04379]
443219  JUN; transcription factor Jun [KO:K04448]
443342  IL10; interleukin-10 precursor [KO:K05443]
443350  IL5; interleukin-5 precursor [KO:K05428]
443396  IFNG; interferon gamma precursor [KO:K04687]
443397  CD3D; T-cell surface glycoprotein CD3 delta chain precursor [KO:K06450]
443398  [KO:K06452]
443400  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
443401  IL2; interleukin-2 precursor [KO:K05429]
443436  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
443437  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
443480  CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
443509  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
443540  TNF; tumor necrosis factor [KO:K03156]
767628  CD40LG; CD40 ligand [KO:K03161]
780484  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
780520  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
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
oas04010  MAPK signaling pathway
oas04020  Calcium signaling pathway
oas04064  NF-kappa B signaling pathway
oas04120  Ubiquitin mediated proteolysis
oas04151  PI3K-Akt signaling pathway
oas04514  Cell adhesion molecules
oas04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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