KEGG   PATHWAY: mmu04660
Entry
mmu04660                    Pathway                                
Name
T cell receptor signaling pathway - Mus musculus (house mouse)
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
mmu04660  T cell receptor signaling pathway
mmu04660

Other DBs
GO: 0050852
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
12500  Cd3d; CD3 antigen, delta polypeptide [KO:K06450]
12501  Cd3e; CD3 antigen, epsilon polypeptide [KO:K06451]
12502  Cd3g; CD3 antigen, gamma polypeptide [KO:K06452]
12503  Cd247; CD247 antigen [KO:K06453]
12504  Cd4; CD4 antigen [KO:K06454]
12525  Cd8a; CD8 subunit alpha [KO:K06458]
12526  Cd8b1; CD8 subunit beta 1 [KO:K06459]
19264  Ptprc; protein tyrosine phosphatase receptor type C [KO:K06478] [EC:3.1.3.48]
16818  Lck; lymphocyte protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
14360  Fyn; Fyn proto-oncogene [KO:K05703] [EC:2.7.10.2]
22637  Zap70; zeta-chain (TCR) associated protein kinase [KO:K07360] [EC:2.7.10.2]
16822  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
16797  Lat; linker for activation of T cells [KO:K07362]
16428  Itk; IL2 inducible T cell kinase [KO:K07363] [EC:2.7.10.2]
21682  Tec; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
17973  Nck1; non-catalytic region of tyrosine kinase adaptor protein 1 [KO:K07365]
17974  Nck2; non-catalytic region of tyrosine kinase adaptor protein 2 [KO:K19862]
22324  Vav1; vav 1 oncogene [KO:K05730]
22325  Vav2; vav 2 oncogene [KO:K05730]
57257  Vav3; vav 3 oncogene [KO:K05730]
17444  Grap2; GRB2-related adaptor protein 2 [KO:K07366]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
18479  Pak1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
224105  Pak2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:2.7.11.1]
18481  Pak3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:2.7.11.1]
70584  Pak4; p21 (RAC1) activated kinase 4 [KO:K05734] [EC:2.7.11.1]
241656  Pak5; p21 (RAC1) activated kinase 5 [KO:K05736] [EC:2.7.11.1]
214230  Pak6; p21 (RAC1) activated kinase 6 [KO:K05735] [EC:2.7.11.1]
11848  Rhoa; ras homolog family member A [KO:K04513]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
12540  Cdc42; cell division cycle 42 [KO:K04393]
13383  Dlg1; discs large MAGUK scaffold protein 1 [KO:K12076]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
19055  Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19057  Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19058  Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
18018  Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
18019  Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18021  Nfatc3; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 3 [KO:K17333]
20662  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
20663  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
19419  Rasgrp1; RAS guanyl releasing protein 1 [KO:K04350]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
16476  Jun; jun proto-oncogene [KO:K04448]
18761  Prkcq; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
108723  Card11; caspase recruitment domain family, member 11 [KO:K07367]
12042  Bcl10; B cell leukemia/lymphoma 10 [KO:K07368]
240354  Malt1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
26400  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18036  Nfkbib; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta [KO:K02581]
18037  Nfkbie; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, epsilon [KO:K05872]
12487  Cd28; CD28 antigen [KO:K06470]
54167  Icos; inducible T cell co-stimulator [KO:K06713]
21947  Cd40lg; CD40 ligand [KO:K03161]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18607  Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
26410  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
53859  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
18566  Pdcd1; programmed cell death 1 [KO:K06744]
12477  Ctla4; cytotoxic T-lymphocyte-associated protein 4 [KO:K06538]
15170  Ptpn6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
19247  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:3.1.3.16]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
269643  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
52432  Ppp2r2d; protein phosphatase 2, regulatory subunit B, delta [KO:K04354]
71978  Ppp2r2a; protein phosphatase 2, regulatory subunit B, alpha [KO:K04354]
72930  Ppp2r2b; protein phosphatase 2, regulatory subunit B, beta [KO:K04354]
100039815  Gm2436; predicted gene 2436 [KO:K11583]
100039830  Gm2446; predicted gene 2446 [KO:K11583]
19054  Ppp2r3d; protein phosphatase 2 (formerly 2A), regulatory subunit B'', delta [KO:K11583]
235542  Ppp2r3a; protein phosphatase 2, regulatory subunit B'', alpha [KO:K11583]
59032  Ppp2r3c; protein phosphatase 2, regulatory subunit B'', gamma [KO:K11583]
21770  Ppp2r5d; protein phosphatase 2, regulatory subunit B', delta [KO:K11584]
225849  Ppp2r5b; protein phosphatase 2, regulatory subunit B', beta [KO:K11584]
226849  Ppp2r5a; protein phosphatase 2, regulatory subunit B', alpha [KO:K11584]
26931  Ppp2r5c; protein phosphatase 2, regulatory subunit B', gamma [KO:K11584]
26932  Ppp2r5e; protein phosphatase 2, regulatory subunit B', epsilon [KO:K11584]
208650  Cblb; Casitas B-lineage lymphoma b [KO:K22517] [EC:2.3.2.27]
16183  Il2; interleukin 2 [KO:K05429]
16189  Il4; interleukin 4 [KO:K05430]
16191  Il5; interleukin 5 [KO:K05428]
16153  Il10; interleukin 10 [KO:K05443]
15978  Ifng; interferon gamma [KO:K04687]
12981  Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
21926  Tnf; tumor necrosis factor [KO:K03156]
12567  Cdk4; 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
mmu04010  MAPK signaling pathway
mmu04020  Calcium signaling pathway
mmu04064  NF-kappa B signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04151  PI3K-Akt signaling pathway
mmu04514  Cell adhesion molecules
mmu04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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