KEGG   PATHWAY: mun04660
Entry
mun04660                    Pathway                                
Name
T cell receptor signaling pathway - Meriones unguiculatus (Mongolian gerbil)
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
mun04660  T cell receptor signaling pathway
mun04660

Other DBs
GO: 0050852
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110549118  T-cell surface glycoprotein CD3 delta chain [KO:K06450]
110549111  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
110549119  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
110562425  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
110548574  Cd4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
110562260  Cd8a; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
110562253  Cd8b; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
110560152  Ptprc; receptor-type tyrosine-protein phosphatase C isoform X3 [KO:K06478] [EC:3.1.3.48]
110548547  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
110561016  Fyn; tyrosine-protein kinase Fyn isoform X3 [KO:K05703] [EC:2.7.10.2]
110545437  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
110545366  Lcp2; lymphocyte cytosolic protein 2 isoform X3 [KO:K07361]
110548013  Lat; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
110554048  Itk; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
110558816  Tec; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
110555024  Nck1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
110559035  Nck2; cytoplasmic protein NCK2 [KO:K19862]
110557506  Vav2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
110545611  Vav1; proto-oncogene vav isoform X1 [KO:K05730]
110547752  Vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
110550441  Grap2; GRB2-related adapter protein 2 [KO:K07366]
110547825  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
110547315  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
110553293  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
110541384  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
110552542  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
110540522  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
110550597  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
110540728  transforming protein RhoA-like isoform X1 [KO:K04513]
110565123  Rhoa; transforming protein RhoA isoform X2 [KO:K04513]
110545010  Cdc42; cell division control protein 42 homolog isoform X2 [KO:K04393]
110553298  Dlg1; disks large homolog 1 isoform X8 [KO:K12076]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110552794  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110555973  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
110551992  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
110551668  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
110558957  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
110561325  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
110550273  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
110547352  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
110545902  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
110547073  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110556913  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110565085  Rasgrp1; RAS guanyl-releasing protein 1 [KO:K04350]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110544642  GTPase NRas [KO:K07828]
110544765  Nras; GTPase NRas [KO:K07828]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110546962  Fos; protein c-Fos [KO:K04379]
110559727  Jun; transcription factor Jun [KO:K04448]
110556894  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
110554731  Card11; caspase recruitment domain-containing protein 11 [KO:K07367]
110558307  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
110546634  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
110565808  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
132650544  Map2k7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110544653  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110552558  Nfkbib; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
110555836  Nfkbie; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
110554770  Cd28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
110562837  Icos; LOW QUALITY PROTEIN: inducible T-cell costimulator [KO:K06713]
110561796  Cd40lg; CD40 ligand [KO:K03161]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110553013  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110558401  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
110545661  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
110545716  Pdcd1; programmed cell death protein 1 isoform X1 [KO:K06744]
110554772  Ctla4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
110548584  Ptpn6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
110546380  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
110549625  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
110548328  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
110560607  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
110565703  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
110549018  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
110544846  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma isoform X2 [KO:K04354]
110564033  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
110559335  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
110553748  Ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
110559682  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
110565800  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
110556971  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
110550362  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
110549337  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
110553236  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
110557573  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
110540535  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
110545874  Il2; interleukin-2 [KO:K05429]
110560079  interleukin-2-like [KO:K05429]
110548759  Il4; interleukin-4 [KO:K05430]
110548757  Il5; interleukin-5 [KO:K05428]
110550319  Il10; interleukin-10 [KO:K05443]
110561827  Ifng; interferon gamma [KO:K04687]
110561713  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
110560136  Tnf; LOW QUALITY PROTEIN: tumor necrosis factor [KO:K03156]
110561245  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
mun04010  MAPK signaling pathway
mun04020  Calcium signaling pathway
mun04064  NF-kappa B signaling pathway
mun04120  Ubiquitin mediated proteolysis
mun04151  PI3K-Akt signaling pathway
mun04514  Cell adhesion molecules
mun04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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