KEGG   PATHWAY: ko04660Help
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
BRITE hierarchy
Pathway map
T cell receptor signaling pathway
ko04660

All organismsOrtholog table
Disease
H00408  
Type I diabetes mellitus
H00540  
Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  
Incontinentia pigmenti
H00882  
Cocoon syndrome
H01387  
Activated PI3K-delta syndrome (APDS)
Other DBs
BSID: 
GO: 
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  
CD4 antigen
K06458  
CD8A antigen, alpha polypeptide
K06459  
CD8B antigen, beta polypeptide
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
K05730  
guanine nucleotide exchange factor VAV
K07366  
GRB2-related adaptor protein 2
K04364  
growth factor receptor-binding 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]
K05735  
p21-activated kinase 6 [EC:2.7.11.1]
K05736  
p21-activated kinase 7 [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]
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
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [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]
K04707  
E3 ubiquitin-protein ligase CBL [EC:6.3.2.19]
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)
Reference
  Authors
Macian F.
  Title
NFAT proteins: key regulators of T-cell development and function.
  Journal
Nat Rev Immunol 5:472-84 (2005)
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)
Reference
  Authors
Huang Y, Wange RL.
  Title
T cell receptor signaling: beyond complex complexes.
  Journal
J Biol Chem 279:28827-30 (2004)
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)
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)
Reference
  Authors
Horejsi V, Zhang W, Schraven B.
  Title
Transmembrane adaptor proteins: organizers of immunoreceptor signalling.
  Journal
Nat Rev Immunol 4:603-16 (2004)
Reference
  Authors
Baniyash M.
  Title
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response.
  Journal
Nat Rev Immunol 4:675-87 (2004)
Reference
  Authors
Sechi AS, Wehland J.
  Title
Interplay between TCR signalling and actin cytoskeleton dynamics.
  Journal
Trends Immunol 25:257-65 (2004)
Reference
  Authors
Okkenhaug K, Vanhaesebroeck B.
  Title
PI3K in lymphocyte development, differentiation and activation.
  Journal
Nat Rev Immunol 3:317-30 (2003)
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)
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)
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)
Reference
  Authors
Finkelstein LD, Schwartzberg PL.
  Title
Tec kinases: shaping T-cell activation through actin.
  Journal
Trends Cell Biol 14:443-51 (2004)
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)
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)
Reference
  Authors
Smith-Garvin JE, Koretzky GA, Jordan MS
  Title
T Cell Activation.
  Journal
Annu Rev Immunol (2009)
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)
Reference
  Authors
Blonska M, Lin X
  Title
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.
  Journal
Immunol Rev 228:199-211 (2009)
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)
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)
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)

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