Entry 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 systemBRITE hierarchy
Pathway map ko04660 T cell receptor signaling pathway
Other DBs Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581 NFKBIB; NF-kappa-B inhibitor beta
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03161 TNFSF5, CD40L, CD154; tumor necrosis factor ligand superfamily member 5
K03456 PPP2R1; serine/threonine-protein phosphatase 2A regulatory subunit A
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04350 RASGRP1; RAS guanyl-releasing protein 1
K04354 PPP2R2; serine/threonine-protein phosphatase 2A regulatory subunit B
K04364 GRB2; growth factor receptor-bound protein 2
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04379 FOS; proto-oncogene protein c-fos
K04382 PPP2C; serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16 ]
K04393 CDC42; cell division control protein 42
K04415 MAP3K8, COT; mitogen-activated protein kinase kinase kinase 8 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04466 MAP3K14, NIK; mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04513 RHOA; Ras homolog gene family, member A
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05427 CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor
K05443 IL10, CSIF; interleukin 10
K05697 PTPN6, SHP1; tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48 ]
K05730 VAV; guanine nucleotide exchange factor VAV
K05856 LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2 ]
K05872 NFKBIE; NF-kappa-B inhibitor epsilon
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06276 PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1 ]
K06450 CD3D; T-cell surface glycoprotein CD3 delta chain
K06451 CD3E; T-cell surface glycoprotein CD3 epsilon chain
K06452 CD3G; T-cell surface glycoprotein CD3 gamma chain
K06453 CD3Z, CD247; CD3Z antigen, zeta polypeptide
K06454 CD4; T-cell surface glycoprotein CD4
K06458 CD8A; T-cell surface glycoprotein CD8 alpha chain
K06459 CD8B; T-cell surface glycoprotein CD8 beta chain
K06478 PTPRC, CD45; receptor-type tyrosine-protein phosphatase C [EC:3.1.3.48 ]
K06538 CTLA4, CD152; cytotoxic T-lymphocyte-associated protein 4
K06713 ICOS, AILIM, CD278; inducible T-cell co-stimulator
K06744 PDCD1, PD1, CD279; programmed cell death protein 1
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07293 PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48 ]
K07361 LCP2; lymphocyte cytosolic protein 2
K07362 LAT; linker for activation of T cells family member 1
K07365 NCK1; NCK adaptor protein 1
K07366 GRAP2, GADS; GRB2-related adaptor protein 2
K07367 CARD11; caspase recruitment domain-containing protein 11
K07368 BCL10; B-cell CLL/lymphoma 10
K07369 MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-]
K07827 KRAS, KRAS2; GTPase KRas
K10784 TRAV; T cell receptor alpha chain V region
K10785 TRBV; T-cell receptor beta chain V region
K11583 PPP2R3; serine/threonine-protein phosphatase 2A regulatory subunit B''
K11584 PPP2R5; serine/threonine-protein phosphatase 2A regulatory subunit B'
K12076 DLG1; disks large protein 1
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333 NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K19862 NCK2, GRB4; NCK adaptor protein 2
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 ko04064 NF-kappa B signaling pathway
ko04120 Ubiquitin mediated proteolysis
ko04810 Regulation of actin cytoskeleton
