KEGG   PATHWAY: rno04660
Entry
rno04660                    Pathway                                
Name
T cell receptor signaling pathway - Rattus norvegicus (rat)
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
rno04660  T cell receptor signaling pathway
rno04660

Other DBs
GO: 0050852
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25710  Cd3d; T-cell surface glycoprotein CD3 delta chain precursor [KO:K06450]
315609  Cd3e; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
300678  Cd3g; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452]
25300  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform 2 precursor [KO:K06453]
24932  Cd4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
24930  Cd8a; T-cell surface glycoprotein CD8 alpha chain precursor [KO:K06458]
24931  Cd8b; T-cell surface glycoprotein CD8 beta chain precursor [KO:K06459]
24699  Ptprc; receptor-type tyrosine-protein phosphatase C isoform 4 precursor [KO:K06478] [EC:3.1.3.48]
313050  Lck; proto-oncogene tyrosine-protein kinase LCK [KO:K05856] [EC:2.7.10.2]
25150  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
301348  Zap70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
155918  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
81511  Lat; linker for activation of T-cells family member 1 [KO:K07362]
363577  Itk; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
84492  Tec; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
300955  Nck1; cytoplasmic protein NCK1 [KO:K07365]
316369  Nck2; cytoplasmic protein NCK2 [KO:K19862]
25156  Vav1; proto-oncogene vav [KO:K05730]
295378  Vav3; guanine nucleotide exchange factor VAV3 [KO:K05730]
296603  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
366962  Grap2; GRB2-related adapter protein 2 [KO:K07366]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
29431  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
29432  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
29433  Pak3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
292756  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
311450  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
296078  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
25252  Dlg1; disks large homolog 1 isoform 1 [KO:K12076]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
100361818  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446]
311658  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
361400  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
29434  Rasgrp1; RAS guanyl-releasing protein 1 [KO:K04350]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
314322  Fos; protein c-Fos [KO:K04379]
24516  Jun; transcription factor Jun [KO:K04448]
85420  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
100363332  Card11; caspase recruitment domain-containing protein 11 [KO:K07367]
83477  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
307366  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform 1 [KO:K07369] [EC:3.4.22.-]
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431] [EC:2.7.12.2]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
316241  Nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
25660  Cd28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
64545  Icos; inducible T-cell costimulator precursor [KO:K06713]
84349  Cd40lg; CD40 ligand [KO:K03161]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116596  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
360640  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
301626  Pdcd1; programmed cell death protein 1 precursor [KO:K06744]
63835  Ctla4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
116689  Ptpn6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
25622  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform 2 [KO:K07293] [EC:3.1.3.48]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
246255  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
60660  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform 1 [KO:K04354]
117256  Ppp2r2c; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform 1 [KO:K04354]
117104  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
682033  Ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
362739  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
363122  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
309179  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
691318  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform 4 [KO:K11584]
363193  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
299147  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
312754  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
171136  Cblb; E3 ubiquitin-protein ligase CBL-B [KO:K22517] [EC:2.3.2.27]
116562  Il2; interleukin-2 precursor [KO:K05429]
287287  Il4; interleukin-4 precursor [KO:K05430]
24497  Il5; interleukin-5 precursor [KO:K05428]
25325  Il10; interleukin-10 precursor [KO:K05443]
25712  Ifng; interferon gamma precursor [KO:K04687]
116630  Csf2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
24835  Tnf; tumor necrosis factor [KO:K03156]
94201  Cdk4; cyclin-dependent kinase 4 isoform 1 [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
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04064  NF-kappa B signaling pathway
rno04120  Ubiquitin mediated proteolysis
rno04151  PI3K-Akt signaling pathway
rno04514  Cell adhesion molecules
rno04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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