KEGG   PATHWAY: dro04660
Entry
dro04660                    Pathway                                

Name
T cell receptor signaling pathway - Desmodus rotundus (common vampire 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
dro04660  T cell receptor signaling pathway
dro04660

Other DBs
GO: 0050852
Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112314228  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
112314382  CD3E; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
112314387  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
112321742  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
112322003  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
112302983  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
112302981  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
112318902  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
112299317  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
112297021  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
112315209  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
112319500  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
112304844  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
112319647  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
112316881  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
112309536  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
112315145  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
112313799  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
112312402  VAV1; proto-oncogene vav [KO:K05730]
112306573  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
112321921  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
112298645  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112316047  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
112320635  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
112296895  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
112320090  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
112303959  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
112311615  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
112309492  RHOA; transforming protein RhoA [KO:K04513]
112307557  transforming protein RhoA-like isoform X1 [KO:K04513]
112299195  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
112320513  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
112302047  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112321896  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112302140  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112322057  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
112303845  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
112305449  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112317863  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
112305248  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112297858  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
112304508  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
112322654  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
112303992  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
112300806  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
112297971  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112310995  SOS2; son of sevenless homolog 2 [KO:K03099]
112311978  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112304041  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
112313707  NRAS; GTPase NRas [KO:K07828]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112311412  FOS; proto-oncogene c-Fos [KO:K04379]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112320743  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
112319699  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
112309355  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
112322863  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
112296959  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
112305131  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112317202  RELA; transcription factor p65 [KO:K04735]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112320245  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
112302226  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
112307972  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
112307652  ICOS; inducible T-cell costimulator [KO:K06713]
112307303  CD40LG; CD40 ligand isoform X1 [KO:K03161]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112314466  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112298319  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112316842  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
112298609  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
112320540  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
112308039  PDCD1; programmed cell death protein 1 [KO:K06744]
112307993  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
112321823  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
112320522  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
112312503  IL2; interleukin-2 [KO:K05429]
112318159  IL4; interleukin-4 [KO:K05430]
112318060  IL5; LOW QUALITY PROTEIN: interleukin-5 [KO:K05428]
112315005  IL10; interleukin-10 [KO:K05443]
112319176  IFNG; interferon gamma [KO:K04687]
112301620  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
112302067  TNF; tumor necrosis factor isoform X1 [KO:K03156]
112319119  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
  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
dro04010  MAPK signaling pathway
dro04020  Calcium signaling pathway
dro04064  NF-kappa B signaling pathway
dro04120  Ubiquitin mediated proteolysis
dro04151  PI3K-Akt signaling pathway
dro04514  Cell adhesion molecules
dro04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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