KEGG   PATHWAY: umr04660
Entry
umr04660                    Pathway                                
Name
T cell receptor signaling pathway - Ursus maritimus (polar bear)
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
umr04660  T cell receptor signaling pathway
umr04660

Other DBs
GO: 0050852
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656221  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
103656225  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
103656496  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
103656694  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103656765  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
103656858  IFNG; interferon gamma [KO:K04687]
103657330  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X5 [KO:K03456]
103657674  IL10; interleukin-10 [KO:K05443]
103657689  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X3 [KO:K06478] [EC:3.1.3.48]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103657908  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
103658340  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
103658377  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X3 [KO:K04354]
103658473  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
103658916  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103659105  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103659772  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
103659775  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
103659776  ICOS; inducible T-cell costimulator isoform X1 [KO:K06713]
103660092  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103661015  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661079  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
103661289  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
103661804  IL2; interleukin-2 [KO:K05429]
103662336  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
103662337  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
103662338  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
103662531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103662595  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
103662957  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103663691  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
103663832  IL4; interleukin-4 [KO:K05430]
103663836  IL5; interleukin-5 [KO:K05428]
103664144  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
103664157  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103664542  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
103664784  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103665244  KRAS; GTPase KRas isoform X1 [KO:K07827]
103665409  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103665883  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103666113  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
103666328  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
103666444  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
103666578  CDC42; cell division control protein 42 homolog [KO:K04393]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103667447  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
103667825  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103667893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103668498  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
103669173  [KO:K02833]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103669422  NRAS; GTPase NRas [KO:K07828]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103669754  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103669832  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103670075  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
103670505  CSF2; granulocyte-macrophage colony-stimulating factor isoform X1 [KO:K05427]
103670625  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103670861  JUN; transcription factor AP-1 [KO:K04448]
103671011  FOS; proto-oncogene c-Fos [KO:K04379]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103671189  [KO:K07360] [EC:2.7.10.2]
103671340  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
103671471  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X1 [KO:K06458]
103671473  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X1 [KO:K06459]
103671891  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103672380  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103672470  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103672715  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
103672841  CD40LG; CD40 ligand [KO:K03161]
103673291  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
103673318  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103673478  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
103673553  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
103673717  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103674429  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
103674825  RHOA; transforming protein RhoA [KO:K04513]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103675192  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103676251  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
103676304  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
103676366  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103676947  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103676988  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103677350  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
103677943  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103678069  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
103678534  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103678785  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
103678792  NCK1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
103678867  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
103678920  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
103678928  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103679434  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
103679584  RELA; transcription factor p65 [KO:K04735]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103679739  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
103679942  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
103679990  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103681714  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103681888  MAP2K7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103682087  [KO:K07293] [EC:3.1.3.48]
103682322  TNF; tumor necrosis factor [KO:K03156]
121100753  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
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
umr04010  MAPK signaling pathway
umr04020  Calcium signaling pathway
umr04064  NF-kappa B signaling pathway
umr04120  Ubiquitin mediated proteolysis
umr04151  PI3K-Akt signaling pathway
umr04514  Cell adhesion molecules
umr04810  Regulation of actin cytoskeleton
KO pathway
ko04660   

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