KEGG   PATHWAY: pcad04660
Entry
pcad04660                   Pathway                                
Name
T cell receptor signaling pathway - Physeter macrocephalus (sperm whale)
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
pcad04660  T cell receptor signaling pathway
pcad04660

Other DBs
GO: 0050852
Organism
Physeter macrocephalus (sperm whale) [GN:pcad]
Gene
102973173  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
102973226  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102973457  [KO:K07365]
102973585  IL10; interleukin-10 [KO:K05443]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102973743  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
102974010  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
102974041  CD40LG; CD40 ligand [KO:K03161]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102974216  CD28; LOW QUALITY PROTEIN: T-cell-specific surface glycoprotein CD28 [KO:K06470]
102974221  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
102974323  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
102974912  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102975458  JUN; transcription factor Jun [KO:K04448]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102975958  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102976080  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
102976346  VAV1; proto-oncogene vav [KO:K05730]
102976396  TEC; tyrosine-protein kinase Tec isoform X4 [KO:K07364] [EC:2.7.10.2]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102977125  KRAS; GTPase KRas isoform X1 [KO:K07827]
102977193  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
102977392  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102977417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102977531  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102977886  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
102977953  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X2 [KO:K06458]
102977994  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102977998  NCK2; cytoplasmic protein NCK2 isoform X2 [KO:K19862]
102978005  [KO:K04409] [EC:2.7.11.1]
102978462  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
102978702  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102978925  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102979279  [KO:K06451]
102979567  [KO:K06450]
102979605  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
102979922  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
102980039  [KO:K06452]
102980192  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102981258  NCK1; cytoplasmic protein NCK1 [KO:K07365]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102981551  IFNG; interferon gamma [KO:K04687]
102981677  [KO:K03099]
102981768  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
102982040  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
102982453  FOS; protein c-Fos [KO:K04379]
102982641  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
102982768  PRKCQ; protein kinase C theta type isoform X3 [KO:K18052] [EC:2.7.11.13]
102983069  TNF; tumor necrosis factor [KO:K03156]
102983351  IL5; interleukin-5 [KO:K05428]
102983421  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102983610  [KO:K11584]
102983639  RHOA; transforming protein RhoA [KO:K04513]
102983897  IL4; interleukin-4 [KO:K05430]
102984161  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102984521  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102984741  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102985008  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102985179  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
102985262  PAK2; serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
102985349  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
102985526  PDCD1; programmed cell death protein 1 isoform X2 [KO:K06744]
102985759  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
102985951  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102986162  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
102986766  DLG1; disks large homolog 1 isoform X4 [KO:K12076]
102986822  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102987013  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
102987078  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102987506  [KO:K07293] [EC:3.1.3.48]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102988344  [KO:K04446]
102988471  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102988564  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
102988604  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102989111  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102989597  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
102989908  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
102990087  [KO:K04456] [EC:2.7.11.1]
102990302  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
102990654  IL2; interleukin-2 [KO:K05429]
102990815  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X8 [KO:K04348] [EC:3.1.3.16]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102991269  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102991639  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102991742  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
102991774  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431] [EC:2.7.12.2]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102992010  LCK; LOW QUALITY PROTEIN: tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
102992184  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
102992191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102992439  [KO:K07828]
102992659  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
102992700  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102992923  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102993070  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
102993492  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X3 [KO:K04354]
102993777  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X5 [KO:K17332]
102993796  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102994150  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102994407  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
102994715  HRAS; GTPase HRas isoform X2 [KO:K02833]
102994784  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
102994835  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
102995677  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
102995727  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102995931  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102996125  ICOS; inducible T-cell costimulator [KO:K06713]
102996184  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
102996353  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102996375  [KO:K07360] [EC:2.7.10.2]
102996458  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
112065477  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
112067521  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114483947  [KO:K04364]
114484431  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
114485485  [KO:K07210]
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
pcad04010  MAPK signaling pathway
pcad04020  Calcium signaling pathway
pcad04064  NF-kappa B signaling pathway
pcad04120  Ubiquitin mediated proteolysis
pcad04151  PI3K-Akt signaling pathway
pcad04514  Cell adhesion molecule (CAM) interaction
pcad04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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