KEGG   PATHWAY: iti04660
Entry
iti04660                    Pathway                                
Name
T cell receptor signaling pathway - Ictidomys tridecemlineatus (thirteen-lined ground squirrel)
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
iti04660  T cell receptor signaling pathway
iti04660

Other DBs
GO: 0050852
Organism
Ictidomys tridecemlineatus (thirteen-lined ground squirrel) [GN:iti]
Gene
101954284  Rasgrp1; RAS guanyl-releasing protein 1 isoform X2 [KO:K04350]
101954308  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X2 [KO:K06453]
101954731  Jun; transcription factor AP-1 [KO:K04448]
101955103  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101955124  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101955264  Ikbkg; NF-kappa-B essential modulator isoform X5 [KO:K07210]
101955316  Rela; transcription factor p65 [KO:K04735]
101955522  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101955964  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101956879  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
101956880  Map3k8; mitogen-activated protein kinase kinase kinase 8 isoform X2 [KO:K04415] [EC:2.7.11.25]
101956975  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101957333  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101957398  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101957470  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
101957556  Ctla4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
101958010  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101958429  Vav2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730]
101958546  Ppp2cb; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101958680  Cd3e; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
101958947  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101958960  Cd3d; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
101959100  Cdc42; cell division control protein 42 homolog isoform X2 [KO:K04393]
101959248  Cd3g; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
101959284  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
101959358  [KO:K04513]
101959359  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
101959407  Fos; proto-oncogene c-Fos [KO:K04379]
101959670  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
101959966  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
101959985  Hras; GTPase HRas isoform X2 [KO:K02833]
101960354  Ppp3r1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
101960854  Grap2; GRB2-related adapter protein 2 isoform X2 [KO:K07366]
101960867  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101961338  Lat; linker for activation of T-cells family member 1 [KO:K07362]
101962346  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X5 [KO:K06276] [EC:2.7.11.1]
101962360  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101962445  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X2 [KO:K11584]
101962660  [KO:K00922] [EC:2.7.1.153]
101962827  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
101962974  Vav1; proto-oncogene vav [KO:K05730]
101963124  Sos2; son of sevenless homolog 2 [KO:K03099]
101963371  Mapk8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101963453  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101963744  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101963921  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101964114  Kras; GTPase KRas isoform X1 [KO:K07827]
101964300  Ptprc; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
101964684  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101964913  Tnf; tumor necrosis factor [KO:K03156]
101965040  Pak1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101965086  Fyn; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101965101  Mapk13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
101965203  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101965394  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101965711  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
101965781  Cd8b; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
101965867  Ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
101965906  [KO:K00922] [EC:2.7.1.153]
101966065  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
101966078  Cd8a; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
101966144  [KO:K04393]
101966426  Rhoa; transforming protein RhoA [KO:K04513]
101966661  Cblb; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101966799  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
101966932  Cd28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
101966934  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101967027  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]
101967223  Icos; inducible T-cell costimulator [KO:K06713]
101967359  Dlg1; disks large homolog 1 isoform X4 [KO:K12076]
101967440  Card11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
101967608  Il2; interleukin-2 [KO:K05429]
101967809  [KO:K04410] [EC:2.7.11.1]
101968896  [KO:K00922] [EC:2.7.1.153]
101969024  Ifng; interferon gamma [KO:K04687]
101969706  Bcl10; B-cell lymphoma/leukemia 10 [KO:K07368]
101969946  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
101969987  Akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101970348  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X8 [KO:K04348] [EC:3.1.3.16]
101970679  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101970750  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101971159  [KO:K04513]
101971364  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101971458  [KO:K07360] [EC:2.7.10.2]
101971730  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
101971784  Malt1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X2 [KO:K07369] [EC:3.4.22.-]
101971957  Cd4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
101972098  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101972359  [KO:K07367]
101972569  Cd40lg; CD40 ligand isoform X1 [KO:K03161]
101972573  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
101972847  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X4 [KO:K11584]
101972903  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101972917  Prkcq; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
101973115  Pdcd1; programmed cell death protein 1 isoform X2 [KO:K06744]
101973345  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101973410  Tec; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
101973690  Nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
101973809  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
101974157  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101974589  Il5; interleukin-5 [KO:K05428]
101974776  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101975090  [KO:K04354]
101975154  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
101975227  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X3 [KO:K11583]
101975512  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101975748  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101975906  Nras; GTPase NRas [KO:K07828]
101976082  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101976177  Il10; interleukin-10 [KO:K05443]
101976353  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101976523  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101976552  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101976824  [KO:K17332]
101976851  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101976909  Nck1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
101977333  Ptpn6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
101977585  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101977647  Itk; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
101977694  Vav3; guanine nucleotide exchange factor VAV3 isoform X2 [KO:K05730]
101977768  Cdk4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101977794  Nck2; cytoplasmic protein NCK2 [KO:K19862]
101977831  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
101978230  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101978265  Pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
101978426  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
101978549  Mapk9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
110598275  [KO:K10785]
120891809  [KO:K10785]
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
iti04010  MAPK signaling pathway
iti04020  Calcium signaling pathway
iti04064  NF-kappa B signaling pathway
iti04120  Ubiquitin mediated proteolysis
iti04151  PI3K-Akt signaling pathway
iti04514  Cell adhesion molecules
iti04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

DBGET integrated database retrieval system