KEGG   PATHWAY: ko04660
Entry
ko04660                     Pathway                                

Name
T cell receptor signaling pathway
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
ko04660  T cell receptor signaling pathway
ko04660

Other DBs
GO: 0050852
Orthology
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K06450  T-cell surface glycoprotein CD3 delta chain
K06451  T-cell surface glycoprotein CD3 epsilon chain
K06452  T-cell surface glycoprotein CD3 gamma chain
K06453  CD3Z antigen, zeta polypeptide
K06454  T-cell surface glycoprotein CD4
K06458  T-cell surface glycoprotein CD8 alpha chain
K06459  T-cell surface glycoprotein CD8 beta chain
K06478  receptor-type tyrosine-protein phosphatase C [EC:3.1.3.48]
K05856  lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2]
K05703  tyrosine-protein kinase Fyn [EC:2.7.10.2]
K07360  tyrosine-protein kinase ZAP-70 [EC:2.7.10.2]
K07361  lymphocyte cytosolic protein 2
K07362  linker for activation of T cells
K07363  IL2-inducible T-cell kinase [EC:2.7.10.2]
K07364  tyrosine-protein kinase Tec [EC:2.7.10.2]
K07365  NCK adaptor protein 1
K19862  NCK adaptor protein 2
K05730  guanine nucleotide exchange factor VAV
K07366  GRB2-related adaptor protein 2
K04364  growth factor receptor-bound protein 2
K04409  p21-activated kinase 1 [EC:2.7.11.1]
K04410  p21-activated kinase 2 [EC:2.7.11.1]
K05733  p21-activated kinase 3 [EC:2.7.11.1]
K05734  p21-activated kinase 4 [EC:2.7.11.1]
K05736  p21-activated kinase 5 [EC:2.7.11.1]
K05735  p21-activated kinase 6 [EC:2.7.11.1]
K04513  Ras homolog gene family, member A
K04393  cell division control protein 42
K12076  disks large protein 1
K04441  p38 MAP kinase [EC:2.7.11.24]
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K17333  nuclear factor of activated T-cells, cytoplasmic 3
K03099  son of sevenless
K04350  RAS guanyl-releasing protein 1
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  proto-oncogene protein c-fos
K04448  transcription factor AP-1
K18052  novel protein kinase C theta type [EC:2.7.11.13]
K07367  caspase recruitment domain-containing protein 11
K07368  B-cell CLL/lymphoma 10
K07369  mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-]
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04431  mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04734  NF-kappa-B inhibitor alpha
K02581  NF-kappa-B inhibitor beta
K05872  NF-kappa-B inhibitor epsilon
K06470  CD28 antigen
K06713  inducible T-cell co-stimulator
K03161  tumor necrosis factor ligand superfamily member 5
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K06276  3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04415  mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25]
K04466  mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25]
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K06744  programmed cell death protein 1
K06538  cytotoxic T-lymphocyte-associated protein 4
K05697  tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48]
K22517  E3 ubiquitin-protein ligase CBL-B [EC:2.3.2.27]
K05429  interleukin 2
K05430  interleukin 4
K05428  interleukin 5
K05443  interleukin 10
K04687  interferon gamma
K05427  granulocyte-macrophage colony-stimulating factor
K03156  tumor necrosis factor superfamily, member 2
K02089  cyclin-dependent kinase 4 [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
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04064  NF-kappa B signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04151  PI3K-Akt signaling pathway
ko04514  Cell adhesion molecules
ko04810  Regulation of actin cytoskeleton

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