KEGG   PATHWAY: mlf04660
Entry
mlf04660                    Pathway                                
Name
T cell receptor signaling pathway - Myotis lucifugus (little brown 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
mlf04660  T cell receptor signaling pathway
mlf04660

Other DBs
GO: 0050852
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102417312  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4 [KO:K07209] [EC:2.7.11.10]
102417411  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
102417433  FOS; proto-oncogene c-Fos [KO:K04379]
102417642  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
102417755  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102417802  VAV1; proto-oncogene vav [KO:K05730]
102418059  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102418507  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102418755  [KO:K07360] [EC:2.7.10.2]
102419062  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
102419324  [KO:K02649]
102419342  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
102420162  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102420569  PAK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
102420806  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102420915  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
102421027  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102421207  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102421330  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102421388  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102422214  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
102422236  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102422264  RHOA; transforming protein RhoA [KO:K04513]
102422347  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102422649  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102422740  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
102423271  [KO:K04354]
102423748  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102423786  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
102423936  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
102424236  RELA; transcription factor p65 [KO:K04735]
102424973  [KO:K19862]
102425603  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102425850  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
102426106  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102426111  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102427698  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
102427887  CD247; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
102427890  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102428034  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
102428104  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102428507  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102428565  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
102428794  GSK3B; glycogen synthase kinase-3 beta isoform X13 [KO:K03083] [EC:2.7.11.26]
102428803  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102428805  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
102429230  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102429407  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102429748  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102430062  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X5 [KO:K11584]
102430192  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102430582  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102430744  NRAS; GTPase NRas [KO:K07828]
102430746  [KO:K04513]
102430773  IL5; interleukin-5 [KO:K05428]
102430803  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
102431174  IL10; interleukin-10 [KO:K05443]
102431175  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
102431196  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102431421  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
102431483  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
102431735  PTPN6; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
102431798  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102431999  KRAS; GTPase KRas isoform X1 [KO:K07827]
102432188  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102432497  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102432845  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102432946  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
102433200  IL2; interleukin-2 [KO:K05429]
102433204  CD40LG; CD40 ligand [KO:K03161]
102433480  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102433534  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102433629  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
102434410  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102434453  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102435748  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102436137  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
102436309  NCK1; cytoplasmic protein NCK1 [KO:K07365]
102436423  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
102436424  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102436485  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
102436522  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
102436834  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
102437363  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
102437415  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102437455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437531  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
102437558  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102437928  IL4; interleukin-4 [KO:K05430]
102437934  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102438044  PAK3; serine/threonine-protein kinase PAK 3 isoform X4 [KO:K05733] [EC:2.7.11.1]
102438171  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
102438564  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
102438862  ICOS; inducible T-cell costimulator [KO:K06713]
102438914  [KO:K04441] [EC:2.7.11.24]
102438946  IFNG; interferon gamma [KO:K04687]
102438976  CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X2 [KO:K06451]
102439024  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102439304  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
102439580  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
102439923  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102440385  [KO:K04354]
102440593  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
102440792  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
102441003  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102441064  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102441522  [KO:K02649]
102441857  NFATC2; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
102441944  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
102442817  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102442926  SOS1; son of sevenless homolog 1 [KO:K03099]
102442935  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
102443084  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
102443221  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102443279  [KO:K04456] [EC:2.7.11.1]
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
mlf04010  MAPK signaling pathway
mlf04020  Calcium signaling pathway
mlf04064  NF-kappa B signaling pathway
mlf04120  Ubiquitin mediated proteolysis
mlf04151  PI3K-Akt signaling pathway
mlf04514  Cell adhesion molecule (CAM) interaction
mlf04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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