KEGG   PATHWAY: ocu04660
Entry
ocu04660                    Pathway                                
Name
T cell receptor signaling pathway - Oryctolagus cuniculus (rabbit)
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
ocu04660  T cell receptor signaling pathway
ocu04660

Other DBs
GO: 0050852
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
108178285  uncharacterized protein LOC108178285 [KO:K10784]
100356153  T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
100339529  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
100008616  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
100355340  T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
100352809  T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
100008617  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
100009152  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
100356269  T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
100355767  T-cell surface glycoprotein CD8 beta chain [KO:K06459]
100358807  receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
100349102  tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
100339741  tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100342021  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
100339465  lymphocyte cytosolic protein 2 [KO:K07361]
100350076  linker for activation of T-cells family member 1 isoform X2 [KO:K07362]
100351986  tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
100341923  tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
100358703  cytoplasmic protein NCK1 isoform X2 [KO:K07365]
100353755  cytoplasmic protein NCK2 [KO:K19862]
100341627  guanine nucleotide exchange factor VAV3 [KO:K05730]
103352473  GRB2-related adapter protein 2 isoform X1 [KO:K07366]
100342500  growth factor receptor-bound protein 2 [KO:K04364]
100352056  serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
100009535  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
100347273  serine/threonine-protein kinase PAK 3 isoform X2 [KO:K05733] [EC:2.7.11.1]
100341934  serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
100340742  serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
100348921  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
100356250  transforming protein RhoA [KO:K04513]
100348967  transforming protein RhoA-like [KO:K04513]
100340661  transforming protein RhoA [KO:K04513]
100346856  LOW QUALITY PROTEIN: transforming protein RhoA [KO:K04513]
100343368  transforming protein RhoA-like [KO:K04513]
100343680  transforming protein RhoA-like [KO:K04513]
127489660  transforming protein RhoA-like [KO:K04513]
100008965  cell division control protein 42 homolog isoform X1 [KO:K04393]
100344482  cell division control protein 42 homolog [KO:K04393]
100339253  disks large homolog 1 isoform X8 [KO:K12076]
100350614  mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
103346035  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
100344161  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100341695  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100349958  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
100356245  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100009423  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
100009487  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
100344533  calcineurin subunit B type 2 [KO:K06268]
100352378  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
100353824  nuclear factor of activated T-cells, cytoplasmic 2 isoform X3 [KO:K17332]
100008859  nuclear factor of activated T-cells, cytoplasmic 3 isoform X2 [KO:K17333]
100356615  son of sevenless homolog 1 isoform X1 [KO:K03099]
100346391  son of sevenless homolog 2 isoform X1 [KO:K03099]
100359319  RAS guanyl-releasing protein 1 isoform X2 [KO:K04350]
127486605  GTPase HRas isoform X1 [KO:K02833]
100347487  GTPase KRas isoform X1 [KO:K07827]
127489236  GTPase KRas-like [KO:K07827]
100344241  GTPase NRas [KO:K07828]
100347407  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100009316  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127489461  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
100347345  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100348561  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100338345  protein c-Fos [KO:K04379]
100008856  JUN; transcription factor Jun [KO:K04448]
103350889  protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
100354145  caspase recruitment domain-containing protein 11 [KO:K07367]
100355876  B-cell lymphoma/leukemia 10 [KO:K07368]
100340322  mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
100343571  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103345313  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
100346929  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100342664  mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
100337999  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100355888  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100356401  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5 [KO:K07209] [EC:2.7.11.10]
100328905  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100349426  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127485184  transcription factor p65 isoform X1 [KO:K04735]
100357341  NF-kappa-B inhibitor alpha [KO:K04734]
100359283  NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
100359054  NF-kappa-B inhibitor epsilon [KO:K05872]
100008998  CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
100352250  inducible T-cell costimulator [KO:K06713]
100358388  CD40LG; CD40 ligand [KO:K03161]
100357841  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100345250  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100348663  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100345181  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100337822  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100347954  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100342852  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100353706  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127486116  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100355566  mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
100351032  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100348842  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100343779  programmed cell death protein 1 isoform X1 [KO:K06744]
100009412  CTLA4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
100348648  tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
100339517  tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100009252  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100009300  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100355092  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100355758  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
100328617  PPP2R2C; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
100009139  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
100328616  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
100348286  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
100355159  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X2 [KO:K11583]
100356580  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
100353545  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X2 [KO:K11583]
100009434  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
100346997  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
100009533  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100009216  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
100009215  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100355469  E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
100302458  IL2; interleukin-2 isoform 1 precursor [KO:K05429]
100302454  IL4; interleukin-4 isoform 1 precursor [KO:K05430]
100358075  interleukin-5 [KO:K05428]
100008701  IL10; interleukin-10 precursor [KO:K05443]
100008602  IFNG; interferon gamma precursor [KO:K04687]
100328720  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
100009088  TNF; tumor necrosis factor precursor [KO:K03156]
100009039  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
ocu04010  MAPK signaling pathway
ocu04020  Calcium signaling pathway
ocu04064  NF-kappa B signaling pathway
ocu04120  Ubiquitin mediated proteolysis
ocu04151  PI3K-Akt signaling pathway
ocu04514  Cell adhesion molecules
ocu04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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