KEGG   PATHWAY: hsa04660
hsa04660                    Pathway                                
T cell receptor signaling pathway - Homo sapiens (human)
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.
Organismal Systems; Immune system
Pathway map
hsa04660  T cell receptor signaling pathway

N00683  CD80/CD86-CD28-PI3K signaling pathway
N01106  TCR-PLCG-ITPR signaling pathway
N01165  PDL/PD1-SHP-PI3K signaling pathway
N01579  CD80/CD86-CTLA4-PP2A signaling pathway
N01696  ICOSLG/ICOS-PI3K signaling pathway
D00107  Tacrolimus (USP/INN)
D00184  Cyclosporine (USP)
D03420  Cedelizumab (USAN/INN)
D04603  Ipilimumab (USAN/INN)
D05092  Muromonab-CD3 (JAN/USAN/INN)
D05480  Pimecrolimus (JAN/USAN/INN)
D05610  Priliximab (USAN/INN)
D05777  Ruplizumab (USAN/INN)
D06193  Toralizumab (USAN/INN)
D06314  Visilizumab (USAN/INN)
D06657  Tremelimumab (USAN/INN)
D08556  Tacrolimus (INN)
D08959  Otelixizumab (USAN)
D08976  Pomalidomide (JAN/USAN/INN)
D09013  Teplizumab (USAN/INN)
D09033  Voclosporin (JAN/USAN/INN)
D09190  Anti-human thymocyte immunoglobulin, rabbit (JAN)
D09207  Catumaxomab (INN)
D09325  Blinatumomab (USAN/INN)
D09575  Ibalizumab (USAN/INN)
D09671  Sotrastaurin (USAN/INN)
D09718  Sotrastaurin acetate (USAN)
D10316  Nivolumab (USAN/INN)
D10390  Pidilizumab (USAN/INN)
D10574  Pembrolizumab (USAN)
D10983  Ruclosporin (USAN/INN)
D10993  Tucidinostat (JAN/USAN/INN)
D11108  Cemiplimab (USAN)
D11122  Letolizumab (USAN/INN)
D11366  Dostarlimab (USAN)
D11372  Duvortuxizumab (USAN)
D11433  Vopratelimab (USAN/INN)
D11487  Tislelizumab (USAN/INN)
D11488  Cetrelimab (USAN/INN)
D11489  Cibisatamab (USAN/INN)
D11605  Spartalizumab (USAN/INN)
D11820  Balstilimab (USAN/INN)
D11823  Zalifrelimab (USAN/INN)
D11827  Retifanlimab (USAN)
D11948  Pacmilimab (USAN/INN)
D11992  Pavurutamab (USAN)
D11996  Feladilimab (USAN/INN)
D12007  Ubamatamab (USAN)
D12058  Elranatamab (USAN)
D12063  Zimberelimab (USAN)
D12119  Sintilimab (USAN/INN)
D12180  Talquetamab (USAN/INN)
D12186  Vudalimab (USAN)
D12190  Cadonilimab (USAN/INN)
D12195  Izuralimab (USAN)
D12198  Penpulimab (USAN)
D12202  Toripalimab (USAN/INN)
D12223  Rosnilimab (USAN)
D12231  Peresolimab (USAN)
D12233  Quavonlimab (USAN/INN)
D12296  Tebentafusp (USAN/INN)
D12300  Acazicolcept (USAN/INN)
D12317  Bavunalimab (USAN/INN)
D12332  Zeluvalimab (USAN/INN)
D12347  Volrustomig (USAN)
D12368  Epcoritamab (USAN/INN)
D12448  Botensilimab (USAN/INN)
D12620  Frexalimab (USAN/INN)
D12625  Pegenzileukin (USAN/INN)
D12709  Dalmitamig (USAN)
D12721  Avitotamig (USAN)
D12724  Forimtamig (USAN/INN)
D12751  Serplulimab (INN)
D12762  Soquelitinib (USAN)
D12764  Rilvegostomig (USAN/INN)
D12791  Eciskafusp alfa (USAN/INN)
D12808  Ivonescimab (USAN/INN)
D12833  Lifileucel (USAN/INN)
D12839  Sasanlimab (USAN/INN)
D12850  Imneskibart (USAN)
Other DBs
GO: 0050852
Homo sapiens (human) [GN:hsa]
915  CD3D; CD3 delta subunit of T-cell receptor complex [KO:K06450]
916  CD3E; CD3 epsilon subunit of T-cell receptor complex [KO:K06451]
917  CD3G; CD3 gamma subunit of T-cell receptor complex [KO:K06452]
919  CD247; CD247 molecule [KO:K06453]
920  CD4; CD4 molecule [KO:K06454]
925  CD8A; CD8 subunit alpha [KO:K06458]
926  CD8B; CD8 subunit beta [KO:K06459]
927  CD8B2; CD8B family member 2 [KO:K06459]
5788  PTPRC; protein tyrosine phosphatase receptor type C [KO:K06478] [EC:]
3932  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:]
2534  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:]
7535  ZAP70; zeta chain of T cell receptor associated protein kinase 70 [KO:K07360] [EC:]
3937  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
27040  LAT; linker for activation of T cells [KO:K07362]
3702  ITK; IL2 inducible T cell kinase [KO:K07363] [EC:]
7006  TEC; tec protein tyrosine kinase [KO:K07364] [EC:]
4690  NCK1; NCK adaptor protein 1 [KO:K07365]
8440  NCK2; NCK adaptor protein 2 [KO:K19862]
10451  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
7409  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
7410  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
9402  GRAP2; GRB2 related adaptor protein 2 [KO:K07366]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
5058  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:]
5062  PAK2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:]
5063  PAK3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:]
10298  PAK4; p21 (RAC1) activated kinase 4 [KO:K05734] [EC:]
57144  PAK5; p21 (RAC1) activated kinase 5 [KO:K05736] [EC:]
56924  PAK6; p21 (RAC1) activated kinase 6 [KO:K05735] [EC:]
106821730  BUB1B-PAK6; BUB1B-PAK6 readthrough [KO:K05735] [EC:]
387  RHOA; ras homolog family member A [KO:K04513]
998  CDC42; cell division cycle 42 [KO:K04393]
1739  DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
5335  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
4772  NFATC1; nuclear factor of activated T cells 1 [KO:K04446]
4773  NFATC2; nuclear factor of activated T cells 2 [KO:K17332]
4775  NFATC3; nuclear factor of activated T cells 3 [KO:K17333]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
10125  RASGRP1; RAS guanyl releasing protein 1 [KO:K04350]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
5588  PRKCQ; protein kinase C theta [KO:K18052] [EC:]
84433  CARD11; caspase recruitment domain family member 11 [KO:K07367]
8915  BCL10; BCL10 immune signaling adaptor [KO:K07368]
10892  MALT1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:]
8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4793  NFKBIB; NFKB inhibitor beta [KO:K02581]
4794  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
940  CD28; CD28 molecule [KO:K06470]
29851  ICOS; inducible T cell costimulator [KO:K06713]
959  CD40LG; CD40 ligand [KO:K03161]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
110117499  P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [KO:K02649]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
5170  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
1326  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
5133  PDCD1; programmed cell death 1 [KO:K06744]
1493  CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]
5777  PTPN6; protein tyrosine phosphatase non-receptor type 6 [KO:K05697] [EC:]
5781  PTPN11; protein tyrosine phosphatase non-receptor type 11 [KO:K07293] [EC:]
5515  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:]
5516  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:]
5519  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
5518  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
5520  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
5521  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
5522  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
55844  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
28227  PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
55012  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
5523  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
5526  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
5527  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
5528  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
5529  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
5525  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:]
3558  IL2; interleukin 2 [KO:K05429]
3565  IL4; interleukin 4 [KO:K05430]
3567  IL5; interleukin 5 [KO:K05428]
3586  IL10; interleukin 10 [KO:K05443]
3458  IFNG; interferon gamma [KO:K04687]
1437  CSF2; colony stimulating factor 2 [KO:K05427]
7124  TNF; tumor necrosis factor [KO:K03156]
1019  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:]
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Chen L.
Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity.
Nat Rev Immunol 4:336-47 (2004)
Macian F.
NFAT proteins: key regulators of T-cell development and function.
Nat Rev Immunol 5:472-84 (2005)
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Tec family kinases in T lymphocyte development and function.
Annu Rev Immunol 23:549-600 (2005)
Huang Y, Wange RL.
T cell receptor signaling: beyond complex complexes.
J Biol Chem 279:28827-30 (2004)
Schmitz ML, Bacher S, Dienz O.
NF-kappaB activation pathways induced by T cell costimulation.
FASEB J 17:2187-93 (2003)
Alegre ML, Frauwirth KA, Thompson CB.
T-cell regulation by CD28 and CTLA-4.
Nat Rev Immunol 1:220-8 (2001)
Horejsi V, Zhang W, Schraven B.
Transmembrane adaptor proteins: organizers of immunoreceptor signalling.
Nat Rev Immunol 4:603-16 (2004)
Baniyash M.
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response.
Nat Rev Immunol 4:675-87 (2004)
Sechi AS, Wehland J.
Interplay between TCR signalling and actin cytoskeleton dynamics.
Trends Immunol 25:257-65 (2004)
Okkenhaug K, Vanhaesebroeck B.
PI3K in lymphocyte development, differentiation and activation.
Nat Rev Immunol 3:317-30 (2003)
Palacios EH, Weiss A.
Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
Oncogene 23:7990-8000 (2004)
Kane LP, Lin J, Weiss A.
It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation.
Trends Immunol 23:413-20 (2002)
Acuto O, Michel F.
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Nat Rev Immunol 3:939-51 (2003)
Finkelstein LD, Schwartzberg PL.
Tec kinases: shaping T-cell activation through actin.
Trends Cell Biol 14:443-51 (2004)
Duan L, Reddi AL, Ghosh A, Dimri M, Band H.
The Cbl family and other ubiquitin ligases: destructive forces in control of antigen receptor signaling.
Immunity 21:7-17 (2004)
Schrum AG, Turka LA, Palmer E.
Surface T-cell antigen receptor expression and availability for long-term antigenic signaling.
Immunol Rev 196:7-24 (2003)
Smith-Garvin JE, Koretzky GA, Jordan MS
T cell activation.
Annu Rev Immunol 27:591-619 (2009)
Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, Crabtree GR, Brown PO
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
Proc Natl Acad Sci U S A 99:11796-801 (2002)
Blonska M, Lin X
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.
Immunol Rev 228:199-211 (2009)
Rebeaud F, Hailfinger S, Thome M
Dlgh1 and Carma1 MAGUK proteins contribute to signal specificity downstream of TCR activation.
Trends Immunol 28:196-200 (2007)
Ashwell JD
The many paths to p38 mitogen-activated protein kinase activation in the immune system.
Nat Rev Immunol 6:532-40 (2006)
Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC
Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors.
Nat Immunol 8:154-61 (2007)
hsa04010  MAPK signaling pathway
hsa04020  Calcium signaling pathway
hsa04064  NF-kappa B signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04151  PI3K-Akt signaling pathway
hsa04514  Cell adhesion molecules
hsa04810  Regulation of actin cytoskeleton
KO pathway

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