KEGG   PATHWAY: mna04660
Entry
mna04660                    Pathway                                
Name
T cell receptor signaling pathway - Miniopterus natalensis (Natal long-fingered 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
mna04660  T cell receptor signaling pathway
mna04660

Other DBs
GO: 0050852
Organism
Miniopterus natalensis (Natal long-fingered bat) [GN:mna]
Gene
107523913  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107523964  CBLB; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
107524098  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
107524427  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
107524443  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
107524668  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
107524793  ICOS; inducible T-cell costimulator [KO:K06713]
107524832  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
107524834  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
107525025  IL5; interleukin-5 [KO:K05428]
107525027  IL4; interleukin-4 [KO:K05430]
107525060  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
107525258  KRAS; GTPase KRas [KO:K07827]
107525394  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107525695  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
107525716  VAV1; proto-oncogene vav [KO:K05730]
107525851  SOS2; son of sevenless homolog 2 [KO:K03099]
107525908  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
107526093  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
107526117  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107526728  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
107526881  NCK2; cytoplasmic protein NCK2 [KO:K19862]
107527219  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107527227  IFNG; interferon gamma [KO:K04687]
107527275  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
107527282  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
107527885  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
107527953  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107528331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107528432  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107528628  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
107528645  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
107528876  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
107529052  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
107529317  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107529450  RHOA; transforming protein RhoA [KO:K04513]
107529477  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
107529574  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
107529760  IL2; interleukin-2 [KO:K05429]
107529884  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
107529906  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
107530026  PDCD1; programmed cell death protein 1 [KO:K06744]
107530370  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107530779  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
107530780  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
107530792  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
107531243  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
107531299  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
107532199  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
107532628  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107533349  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
107533364  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
107533446  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
107533544  RELA; transcription factor p65 [KO:K04735]
107533585  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
107533801  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
107533821  FOS; LOW QUALITY PROTEIN: proto-oncogene c-Fos [KO:K04379]
107534103  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107534199  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107534429  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
107534729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107535325  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
107536041  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
107536051  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
107536108  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107536364  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
107536493  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
107536618  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
107536848  NFKBIE; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
107536901  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
107536966  JUN; transcription factor AP-1 [KO:K04448]
107537133  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107537179  [KO:K05730]
107537864  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
107538236  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
107538414  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
107538463  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
107538974  TNF; tumor necrosis factor [KO:K03156]
107539442  IL10; interleukin-10 [KO:K05443]
107539933  CD40LG; CD40 ligand [KO:K03161]
107540236  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
107540441  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107540684  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
107540891  [KO:K04393]
107541020  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
107541106  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107541160  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
107541170  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107541561  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
107541780  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107542012  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
107542131  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
107542351  HRAS; GTPase HRas isoform X1 [KO:K02833]
107542383  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107542423  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
107542460  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
107542599  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
107542952  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
107543032  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
107543203  BCL10; B-cell lymphoma/leukemia 10 isoform X1 [KO:K07368]
107543924  [KO:K07360] [EC:2.7.10.2]
107544013  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
107544062  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
107544156  IKBKG; NF-kappa-B essential modulator [KO:K07210]
107544471  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
107545227  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
107545303  NRAS; GTPase NRas [KO:K07828]
107545444  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
107545505  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107545508  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107545565  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107545613  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107545671  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
107545813  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107545969  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
107546091  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
107546111  NCK1; cytoplasmic protein NCK1 [KO:K07365]
107546223  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
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
mna04010  MAPK signaling pathway
mna04020  Calcium signaling pathway
mna04064  NF-kappa B signaling pathway
mna04120  Ubiquitin mediated proteolysis
mna04151  PI3K-Akt signaling pathway
mna04514  Cell adhesion molecules
mna04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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