KEGG   PATHWAY: mdt04660
Entry
mdt04660                    Pathway                                
Name
T cell receptor signaling pathway - Myotis daubentonii (Daubenton's bat)
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
mdt04660  T cell receptor signaling pathway
mdt04660

Other DBs
GO: 0050852
Organism
Myotis daubentonii (Daubenton's bat) [GN:mdt]
Gene
132212530  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
132212793  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
132212995  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
132213040  [KO:K07360] [EC:2.7.10.2]
132213118  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
132213277  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
132213451  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
132213788  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
132214229  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
132214434  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
132214715  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
132214826  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
132215436  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
132215459  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
132215517  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132215529  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
132215534  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
132215694  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
132215747  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
132215861  RHOA; transforming protein RhoA [KO:K04513]
132216059  [KO:K04513]
132216103  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
132216708  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
132216889  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132216915  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
132216920  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
132217428  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
132218783  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
132219091  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
132219468  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
132219896  [KO:K04354]
132220480  IL10; interleukin-10 [KO:K05443]
132220662  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
132220881  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
132221210  NRAS; GTPase NRas [KO:K07828]
132221258  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
132221673  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
132221796  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
132222289  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
132222397  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
132222407  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
132222895  [KO:K11584]
132222994  [KO:K11584]
132223870  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
132223899  CD40LG; CD40 ligand [KO:K03161]
132224109  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
132225218  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
132226175  IFNG; interferon gamma [KO:K04687]
132226843  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
132226858  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
132226929  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
132227208  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
132227218  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
132227384  KRAS; GTPase KRas isoform X1 [KO:K07827]
132227827  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
132228444  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132228611  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
132228665  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
132229944  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
132230128  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132230265  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
132230275  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
132230375  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
132230447  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
132230883  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
132231012  JUN; transcription factor Jun [KO:K04448]
132231240  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
132231259  FOS; protein c-Fos [KO:K04379]
132231371  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
132231564  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
132231587  [KO:K04393]
132231710  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132232782  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
132232811  LAT; linker for activation of T-cells family member 1 [KO:K07362]
132232956  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
132233401  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
132233575  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
132234311  IL2; interleukin-2 [KO:K05429]
132234319  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
132234601  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
132234607  [KO:K04456] [EC:2.7.11.1]
132234663  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
132234697  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
132234728  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
132234815  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
132234986  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
132235106  VAV1; proto-oncogene vav [KO:K05730]
132235183  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
132235370  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
132235629  IL5; interleukin-5 isoform X1 [KO:K05428]
132235650  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
132235812  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
132235904  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
132235951  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
132236041  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
132236148  IL4; interleukin-4 [KO:K05430]
132236583  TNF; tumor necrosis factor [KO:K03156]
132236985  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
132237065  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
132237277  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
132237309  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
132237408  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
132237411  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
132237910  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
132237911  ICOS; inducible T-cell costimulator [KO:K06713]
132238149  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
132238450  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
132239073  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
132239164  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
132239239  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
132239362  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
132239635  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
132239710  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
132239948  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
132240482  [KO:K06452]
132240484  [KO:K06450]
132240485  [KO:K06451]
132240540  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
132240692  [KO:K04513]
132240766  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
132241412  RELA; transcription factor p65 isoform X1 [KO:K04735]
132241449  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
132241666  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
132241763  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
132241831  HRAS; GTPase HRas isoform X1 [KO:K02833]
132242766  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
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
mdt04010  MAPK signaling pathway
mdt04020  Calcium signaling pathway
mdt04064  NF-kappa B signaling pathway
mdt04120  Ubiquitin mediated proteolysis
mdt04151  PI3K-Akt signaling pathway
mdt04514  Cell adhesion molecules
mdt04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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