KEGG   PATHWAY: setr04660
Entry
setr04660                   Pathway                                
Name
T cell receptor signaling pathway - Suncus etruscus (white-toothed pygmy shrew)
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
setr04660  T cell receptor signaling pathway
setr04660

Other DBs
GO: 0050852
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
125994825  [KO:K04393]
125995970  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
125996221  TNF; tumor necrosis factor [KO:K03156]
125996324  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125996366  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125996581  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
125997295  [KO:K11584]
125997372  NRAS; GTPase NRas [KO:K07828]
125997407  VAV3; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV3 [KO:K05730]
125998044  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125998595  CD40LG; CD40 ligand [KO:K03161]
125998609  PPP2R3C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
125998702  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
125998704  [KO:K04393]
125999018  SOS2; son of sevenless homolog 2 [KO:K03099]
125999080  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
125999512  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
126000642  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
126001240  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126002199  [KO:K07293] [EC:3.1.3.48]
126003300  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
126003303  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
126003551  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
126003555  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
126003563  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
126004025  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
126004042  FOS; protein c-Fos [KO:K04379]
126004337  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
126004457  IL2; interleukin-2 [KO:K05429]
126004565  IL10; interleukin-10 [KO:K05443]
126005876  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
126005943  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
126006109  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
126006273  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
126006370  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
126006373  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
126006407  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
126006542  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
126006708  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
126006854  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
126006959  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
126008669  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
126008975  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
126009330  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
126010979  JUN; transcription factor Jun [KO:K04448]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126011131  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
126011308  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126011898  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
126011949  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126012121  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
126012126  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
126012157  NCK1; cytoplasmic protein NCK1 [KO:K07365]
126012201  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
126012641  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
126013242  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
126013283  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
126013417  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
126014129  RHOA; LOW QUALITY PROTEIN: transforming protein RhoA [KO:K04513]
126014144  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
126014284  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
126015614  [KO:K06451]
126015663  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
126015813  [KO:K06452]
126015814  [KO:K06450]
126016114  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
126016597  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
126017276  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
126017532  [KO:K04409] [EC:2.7.11.1]
126018108  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
126018299  [KO:K04393]
126018881  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
126019025  RELA; transcription factor p65 [KO:K04735]
126019084  HRAS; GTPase HRas [KO:K02833]
126019129  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
126020311  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
126020581  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
126020954  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
126021920  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
126022183  IFNG; interferon gamma [KO:K04687]
126022235  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
126022427  [KO:K04410] [EC:2.7.11.1]
126022823  KRAS; GTPase KRas isoform X1 [KO:K07827]
126023864  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
126023985  NCK2; cytoplasmic protein NCK2 [KO:K19862]
126024149  [KO:K07360] [EC:2.7.10.2]
126024177  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
126024178  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
126024665  [KO:K04393]
126024674  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
126024722  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
126025968  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
126026205  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
126027342  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
126027544  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
126027603  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
126027696  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
126027762  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
126027793  IL5; interleukin-5 [KO:K05428]
126027877  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
126027984  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
126028133  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126028224  [KO:K04348] [EC:3.1.3.16]
126028368  IL4; interleukin-4 [KO:K05430]
126028736  [KO:K04393]
126029540  LAT; linker for activation of T-cells family member 1 [KO:K07362]
126029670  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
126029893  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
126029978  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126030882  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
126031062  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
126031136  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
126031156  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
126032054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
126032385  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
126032521  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
126033346  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126033612  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
126033690  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
126033704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
126033816  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
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)
DOI:10.1038/nri1349
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
setr04010  MAPK signaling pathway
setr04020  Calcium signaling pathway
setr04064  NF-kappa B signaling pathway
setr04120  Ubiquitin mediated proteolysis
setr04151  PI3K-Akt signaling pathway
setr04514  Cell adhesion molecules
setr04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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