KEGG   PATHWAY: phas04660
Entry
phas04660                   Pathway                                
Name
T cell receptor signaling pathway - Phyllostomus hastatus (greater spear-nosed 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
phas04660  T cell receptor signaling pathway
phas04660

Other DBs
GO: 0050852
Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123804403  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
123804414  NRAS; GTPase NRas [KO:K07828]
123805160  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
123805534  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
123805975  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
123806569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123806766  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123806785  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123806902  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807097  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
123807193  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123807317  HRAS; GTPase HRas isoform X1 [KO:K02833]
123807483  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123807522  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
123807983  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123808019  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
123808039  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
123808110  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123808140  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
123808226  FOS; proto-oncogene c-Fos [KO:K04379]
123808510  [KO:K05735] [EC:2.7.11.1]
123808561  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
123808608  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123809299  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
123809960  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123810433  TNF; tumor necrosis factor isoform X1 [KO:K03156]
123810628  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
123810706  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
123811120  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123811378  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
123811711  NCK2; cytoplasmic protein NCK2 [KO:K19862]
123811731  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
123811734  [KO:K07360] [EC:2.7.10.2]
123811909  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
123812205  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
123812406  KRAS; GTPase KRas isoform X1 [KO:K07827]
123812897  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123812938  IL4; interleukin-4 [KO:K05430]
123812946  IL5; interleukin-5 [KO:K05428]
123812973  IFNG; interferon gamma [KO:K04687]
123813225  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
123813227  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
123813640  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123814106  IL2; interleukin-2 [KO:K05429]
123814146  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
123814364  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123814793  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
123815210  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
123815356  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
123815799  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
123815904  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
123816075  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
123816206  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123816247  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123816520  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
123816833  [KO:K10784]
123817083  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
123817350  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123818226  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
123818512  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
123818568  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
123818673  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
123818852  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
123819099  CD40LG; CD40 ligand [KO:K03161]
123819998  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
123820198  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
123820638  IL10; interleukin-10 [KO:K05443]
123820880  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123820887  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123820995  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
123821502  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
123821592  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
123821614  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
123821751  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
123822258  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123822259  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123823081  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
123823240  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
123823384  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
123823743  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123823806  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
123823859  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
123824185  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123824520  [KO:K04513]
123824527  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123825185  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
123825207  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123825523  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123825544  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
123825630  [KO:K04409] [EC:2.7.11.1]
123826011  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
123826073  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
123826609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
123826750  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123826784  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
123826853  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
123827009  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
123827255  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123828197  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123828291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123828358  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
123828668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
123828790  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
123828916  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
123829080  ICOS; inducible T-cell costimulator [KO:K06713]
123829285  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
123829518  RELA; transcription factor p65 [KO:K04735]
123829552  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
123830018  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
123830380  RHOA; transforming protein RhoA [KO:K04513]
123830444  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
123830555  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
123830565  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123831179  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
123831273  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
123831409  JUN; transcription factor AP-1 [KO:K04448]
123831835  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
123831922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123832115  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
123832297  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123832298  [KO:K02649]
123832435  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
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
phas04010  MAPK signaling pathway
phas04020  Calcium signaling pathway
phas04064  NF-kappa B signaling pathway
phas04120  Ubiquitin mediated proteolysis
phas04151  PI3K-Akt signaling pathway
phas04514  Cell adhesion molecules
phas04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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