KEGG   PATHWAY: ngi04660
Entry
ngi04660                    Pathway                                
Name
T cell receptor signaling pathway - Nannospalax galili (Upper Galilee mountains blind mole 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
ngi04660  T cell receptor signaling pathway
ngi04660

Other DBs
GO: 0050852
Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103748303  Cd3d; CD3d molecule [KO:K06450]
103728619  Cd3e; CD3e molecule [KO:K06451]
103748301  Cd3g; CD3g molecule [KO:K06452]
103739902  Cd247; CD247 molecule [KO:K06453]
103727506  Cd4; CD4 molecule [KO:K06454]
103737047  Cd8a; CD8a molecule [KO:K06458]
103737046  Cd8b; CD8b molecule [KO:K06459]
103731886  Ptprc; protein tyrosine phosphatase, receptor type C [KO:K06478] [EC:3.1.3.48]
103745927  Lck; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
103749533  Fyn; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
103738088  Zap70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
103748176  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
103726413  Lat; linker for activation of T-cells [KO:K07362]
103745463  Itk; IL2 inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
103737874  Tec; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
103740969  Nck1; NCK adaptor protein 1 [KO:K07365]
103726627  Nck2; NCK adaptor protein 2 [KO:K19862]
103737178  Vav1; vav guanine nucleotide exchange factor 1 [KO:K05730]
103742820  Vav2; vav guanine nucleotide exchange factor 2 [KO:K05730]
103745151  guanine nucleotide exchange factor VAV3 [KO:K05730]
103730717  Vav3; vav guanine nucleotide exchange factor 3 [KO:K05730]
103748559  Grap2; GRB2-related adaptor protein 2 [KO:K07366]
103732729  Grb2; growth factor receptor bound protein 2 [KO:K04364]
103743005  Pak1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
103738502  Pak2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:2.7.11.1]
103750017  Pak3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:2.7.11.1]
103750732  Pak4; p21 (RAC1) activated kinase 4 [KO:K05734] [EC:2.7.11.1]
103729196  Pak5; p21 (RAC1) activated kinase 5 [KO:K05736] [EC:2.7.11.1]
103741500  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
103743359  transforming protein RhoA-like [KO:K04513]
103750189  Rhoa; ras homolog family member A [KO:K04513]
103746394  Cdc42; cell division cycle 42 [KO:K04393]
103738531  Dlg1; discs large MAGUK scaffold protein 1 [KO:K12076]
103739660  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103739659  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103735473  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103735474  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103747244  Plcg1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103736944  Ppp3cb; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
103747869  Ppp3cc; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
103728037  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
103734750  Ppp3r1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
103749104  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
103748128  Nfatc1; nuclear factor of activated T-cells 1 [KO:K04446]
103735763  Nfatc2; nuclear factor of activated T-cells 2 [KO:K17332]
103734978  Nfatc3; nuclear factor of activated T-cells 3 [KO:K17333]
103743944  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103731514  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103727451  Rasgrp1; RAS guanyl releasing protein 1 [KO:K04350]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103747342  Fos; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103737138  Jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103727298  Prkcq; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
103748714  Card11; caspase recruitment domain family member 11 [KO:K07367]
103728107  Bcl10; B-cell CLL/lymphoma 10 [KO:K07368]
103751814  Malt1; MALT1 paracaspase [KO:K07369] [EC:3.4.22.-]
103739547  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
103726522  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103735023  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103748972  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103749366  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103743976  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103726621  Ikbkb; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103731232  Ikbkg; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
103728077  Nfkb1; nuclear factor kappa B subunit 1 [KO:K02580]
103724994  Rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103734016  Nfkbia; NFKB inhibitor alpha [KO:K04734]
103750726  Nfkbib; NFKB inhibitor beta [KO:K02581]
103730765  Nfkbie; NFKB inhibitor epsilon [KO:K05872]
103744474  Cd28; CD28 molecule [KO:K06470]
103744475  Icos; inducible T-cell costimulator [KO:K06713]
103740147  Cd40lg; CD40 ligand [KO:K03161]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103743959  Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103747991  Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
103738320  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
103741948  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103730858  Pdcd1; programmed cell death 1 [KO:K06744]
103744425  Ctla4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]
103727492  Ptpn6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
103745559  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103729809  Ppp2ca; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
103743584  Ppp2cb; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
103733889  Ppp2r1b; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
103745507  Ppp2r1a; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
103750638  Ppp2r2c; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
103725821  Ppp2r2d; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
103724526  Ppp2r2b; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
103732390  Ppp2r2a; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
103740963  Ppp2r3a; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
103744720  Ppp2r3c; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
103750111  Ppp2r3b; protein phosphatase 2 regulatory subunit B''beta [KO:K11583]
103738772  Ppp2r5b; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
103747958  Ppp2r5e; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
103727046  Ppp2r5a; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
103727634  Ppp2r5c; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
103730801  Ppp2r5d; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
103747585  Cblb; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
103746951  Il2; interleukin 2 [KO:K05429]
103747047  Il4; interleukin 4 [KO:K05430]
103747045  Il5; interleukin 5 [KO:K05428]
103725974  Il10; interleukin 10 [KO:K05443]
103745085  Ifng; interferon gamma [KO:K04687]
103747042  Csf2; colony stimulating factor 2 [KO:K05427]
103724452  Tnf; tumor necrosis factor [KO:K03156]
103742900  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
ngi04010  MAPK signaling pathway
ngi04020  Calcium signaling pathway
ngi04064  NF-kappa B signaling pathway
ngi04120  Ubiquitin mediated proteolysis
ngi04151  PI3K-Akt signaling pathway
ngi04514  Cell adhesion molecules
ngi04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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