Entry
Name
T cell receptor signaling pathway - Homo sapiens (human)
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
hsa04660 T cell receptor signaling pathway
Network
Element
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
Drug
D05092 Muromonab-CD3 (JAN/USAN/INN)
D05480 Pimecrolimus (JAN/USAN/INN)
D06657 Tremelimumab (USAN/INN)
D08976 Pomalidomide (JAN/USAN/INN)
D09033 Voclosporin (JAN/USAN/INN)
D09190 Anti-human thymocyte immunoglobulin, rabbit (JAN)
D09325 Blinatumomab (USAN/INN)
D09671 Sotrastaurin (USAN/INN)
D09718 Sotrastaurin acetate (USAN)
D10993 Tucidinostat (JAN/USAN/INN)
D11433 Vopratelimab (USAN/INN)
D11487 Tislelizumab (USAN/INN)
D11605 Spartalizumab (USAN/INN)
D11823 Zalifrelimab (USAN/INN)
D12300 Acazicolcept (USAN/INN)
D12448 Botensilimab (USAN/INN)
D12625 Pegenzileukin (USAN/INN)
D12764 Rilvegostomig (USAN/INN)
D12791 Eciskafusp alfa (USAN/INN)
D13168 Pembrolizumab and berahyaluronidase alfa
D13247 Abazistobart (USAN/INN)
D13270 Futermestotug (USAN/INN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10125 RASGRP1; RAS guanyl-releasing protein 1 isoform a [KO:K04350 ]
10451 VAV3; guanine nucleotide exchange factor VAV3 isoform 1 [KO:K05730 ]
10892 MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform a [KO:K07369 ] [EC:3.4.22.-]
1147 CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467 ] [EC:2.7.11.10 ]
1437 CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427 ]
1493 CTLA4; cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor [KO:K06538 ]
1739 DLG1; disks large homolog 1 isoform 1 [KO:K12076 ]
208 AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456 ] [EC:2.7.11.1 ]
27040 LAT; linker for activation of T-cells family member 1 isoform a [KO:K07362 ]
28227 PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583 ]
2885 GRB2; growth factor receptor-bound protein 2 isoform 1 [KO:K04364 ]
29851 ICOS; inducible T-cell costimulator precursor [KO:K06713 ]
3551 IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209 ] [EC:2.7.11.10 ]
3565 IL4; interleukin-4 isoform 1 precursor [KO:K05430 ]
3586 IL10; interleukin-10 isoform 1 precursor [KO:K05443 ]
387 RHOA; transforming protein RhoA isoform 1 precursor [KO:K04513 ]
3937 LCP2; lymphocyte cytosolic protein 2 [KO:K07361 ]
4690 NCK1; SH2/SH3 adapter protein NCK1 isoform 1 [KO:K07365 ]
4772 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform F [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform 1 [KO:K17333 ]
4790 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580 ]
4792 NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734 ]
4793 NFKBIB; NF-kappa-B inhibitor beta isoform 1 [KO:K02581 ]
4794 NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872 ]
5133 PDCD1; programmed cell death protein 1 precursor [KO:K06744 ]
5170 PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform 1 [KO:K06276 ] [EC:2.7.11.1 ]
5290 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649 ]
5296 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
5335 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform b [KO:K01116 ] [EC:3.1.4.11 ]
55012 PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform 1 [KO:K11583 ]
5515 PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform 1 [KO:K04382 ] [EC:3.1.3.16 ]
5516 PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382 ] [EC:3.1.3.16 ]
5518 PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform 1 [KO:K03456 ]
5519 PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform a [KO:K03456 ]
5520 PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform 1 [KO:K04354 ]
5521 PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform e [KO:K04354 ]
5522 PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform a [KO:K04354 ]
5523 PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform 1 [KO:K11583 ]
5525 PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform 1 [KO:K11584 ]
5526 PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584 ]
5527 PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform a [KO:K11584 ]
5528 PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform 1 [KO:K11584 ]
5529 PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform a [KO:K11584 ]
5530 PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform 1 [KO:K04348 ] [EC:3.1.3.16 ]
5532 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform b [KO:K04348 ] [EC:3.1.3.16 ]
5533 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform 2 [KO:K04348 ] [EC:3.1.3.16 ]
5534 PPP3R1; calcineurin subunit B type 1 [KO:K06268 ]
5535 PPP3R2; calcineurin subunit B type 2 [KO:K06268 ]
55844 PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform a [KO:K04354 ]
5604 MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368 ] [EC:2.7.12.2 ]
5605 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369 ] [EC:2.7.12.2 ]
5609 MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform 3 [KO:K04431 ] [EC:2.7.12.2 ]
5777 PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform 1 [KO:K05697 ] [EC:3.1.3.48 ]
5781 PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform 1 [KO:K07293 ] [EC:3.1.3.48 ]
5788 PTPRC; receptor-type tyrosine-protein phosphatase C isoform 1 precursor [KO:K06478 ] [EC:3.1.3.48 ]
5894 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366 ] [EC:2.7.11.1 ]
5970 RELA; transcription factor p65 isoform 1 [KO:K04735 ]
6654 SOS1; son of sevenless homolog 1 isoform 1 [KO:K03099 ]
6655 SOS2; son of sevenless homolog 2 isoform 1 [KO:K03099 ]
6885 MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform B [KO:K04427 ] [EC:2.7.11.25 ]
7409 VAV1; proto-oncogene vav isoform 1 [KO:K05730 ]
7410 VAV2; guanine nucleotide exchange factor VAV2 isoform 1 [KO:K05730 ]
8440 NCK2; cytoplasmic protein NCK2 isoform A [KO:K19862 ]
84433 CARD11; caspase recruitment domain-containing protein 11 [KO:K07367 ]
8503 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
8517 IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210 ]
8915 BCL10; B-cell lymphoma/leukemia 10 isoform 1 [KO:K07368 ]
915 CD3D; T-cell surface glycoprotein CD3 delta chain isoform A precursor [KO:K06450 ]
916 CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451 ]
917 CD3G; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452 ]
919 CD247; T-cell surface glycoprotein CD3 zeta chain isoform 1 precursor [KO:K06453 ]
920 CD4; T-cell surface glycoprotein CD4 isoform 1 precursor [KO:K06454 ]
925 CD8A; T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor [KO:K06458 ]
926 CD8B; T-cell surface glycoprotein CD8 beta chain isoform 5 precursor [KO:K06459 ]
927 CD8B2; T-cell surface glycoprotein CD8 beta-2 chain isoform 1 precursor [KO:K06459 ]
940 CD28; T-cell-specific surface glycoprotein CD28 isoform 1 precursor [KO:K06470 ]
9402 GRAP2; GRB2-related adapter protein 2 isoform 1 [KO:K07366 ]
998 CDC42; cell division control protein 42 homolog isoform 1 precursor [KO:K04393 ]
Compound
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
Reference
Authors
Macian F.
Title
NFAT proteins: key regulators of T-cell development and function.
Journal
Reference
Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Title
Tec family kinases in T lymphocyte development and function.
Journal
Reference
Authors
Huang Y, Wange RL.
Title
T cell receptor signaling: beyond complex complexes.
Journal
Reference
Authors
Schmitz ML, Bacher S, Dienz O.
Title
NF-kappaB activation pathways induced by T cell costimulation.
Journal
Reference
Authors
Alegre ML, Frauwirth KA, Thompson CB.
Title
T-cell regulation by CD28 and CTLA-4.
Journal
Reference
Authors
Horejsi V, Zhang W, Schraven B.
Title
Transmembrane adaptor proteins: organizers of immunoreceptor signalling.
Journal
Reference
Authors
Baniyash M.
Title
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response.
Journal
Reference
Authors
Sechi AS, Wehland J.
Title
Interplay between TCR signalling and actin cytoskeleton dynamics.
Journal
Reference
Authors
Okkenhaug K, Vanhaesebroeck B.
Title
PI3K in lymphocyte development, differentiation and activation.
Journal
Reference
Authors
Palacios EH, Weiss A.
Title
Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
Journal
Reference
Authors
Kane LP, Lin J, Weiss A.
Title
It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation.
Journal
Reference
Authors
Acuto O, Michel F.
Title
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Journal
Reference
Authors
Finkelstein LD, Schwartzberg PL.
Title
Tec kinases: shaping T-cell activation through actin.
Journal
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
Reference
Authors
Schrum AG, Turka LA, Palmer E.
Title
Surface T-cell antigen receptor expression and availability for long-term antigenic signaling.
Journal
Reference
Authors
Smith-Garvin JE, Koretzky GA, Jordan MS
Title
T cell activation.
Journal
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
Reference
Authors
Blonska M, Lin X
Title
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.
Journal
Reference
Authors
Rebeaud F, Hailfinger S, Thome M
Title
Dlgh1 and Carma1 MAGUK proteins contribute to signal specificity downstream of TCR activation.
Journal
Reference
Authors
Ashwell JD
Title
The many paths to p38 mitogen-activated protein kinase activation in the immune system.
Journal
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
Related pathway
hsa04514 Cell adhesion molecule (CAM) interaction
hsa04810 Regulation of actin cytoskeleton
KO pathway