KEGG   PATHWAY: mpuf04660
Entry
mpuf04660                   Pathway                                
Name
T cell receptor signaling pathway - Mustela putorius furo (domestic ferret)
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
mpuf04660  T cell receptor signaling pathway
mpuf04660

Other DBs
GO: 0050852
Organism
Mustela putorius furo (domestic ferret) [GN:mpuf]
Gene
101690739  uncharacterized protein LOC101690739 [KO:K10784]
101686008  uncharacterized protein LOC101686008 [KO:K10785]
101676392  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
101676091  CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
101676687  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
101688570  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
101684487  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
101685563  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
101686033  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
101681059  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
101682422  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
101676005  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101682004  ZAP70; tyrosine-protein kinase ZAP-70 isoform X5 [KO:K07360] [EC:2.7.10.2]
101684070  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101691753  LAT; linker for activation of T-cells family member 1 [KO:K07362]
101682037  ITK; tyrosine-protein kinase ITK/TSK isoform X1 [KO:K07363] [EC:2.7.10.2]
101671579  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
101692377  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
101686891  NCK2; cytoplasmic protein NCK2 [KO:K19862]
101673926  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
101686744  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
101689143  VAV2; guanine nucleotide exchange factor VAV2 isoform X3 [KO:K05730]
101682935  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
101685370  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101670448  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
101676957  PAK2; serine/threonine-protein kinase PAK 2 isoform X1 [KO:K04410] [EC:2.7.11.1]
101687579  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101676200  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
101681141  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
101672230  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
101679891  RHOA; transforming protein RhoA [KO:K04513]
101687739  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101672385  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
101684873  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101692143  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101686271  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101684009  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101685356  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101675854  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101675984  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101682554  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101675380  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101688800  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101673044  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101672676  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101676370  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101681860  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101675757  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101670606  RASGRP1; RAS guanyl-releasing protein 1 [KO:K04350]
101681355  HRAS; GTPase HRas isoform X1 [KO:K02833]
101681333  KRAS; GTPase KRas isoform X3 [KO:K07827]
101683038  NRAS; GTPase NRas [KO:K07828]
101690482  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101680975  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101678743  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101679748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101671073  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101685236  FOS; proto-oncogene c-Fos [KO:K04379]
101680348  JUN; transcription factor AP-1 [KO:K04448]
101686572  PRKCQ; protein kinase C theta type isoform X2 [KO:K18052] [EC:2.7.11.13]
101674806  CARD11; caspase recruitment domain-containing protein 11 isoform X3 [KO:K07367]
101676399  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
101678626  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
101682439  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101690814  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
101672072  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101681349  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101676423  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101680658  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101686932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101671648  IKBKG; NF-kappa-B essential modulator [KO:K07210]
101680542  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101680239  RELA; transcription factor p65 [KO:K04735]
101693829  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101679960  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
101684737  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
101689176  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
101689946  ICOS; inducible T-cell costimulator isoform X1 [KO:K06713]
101681499  CD40LG; CD40 ligand [KO:K03161]
101680399  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101683594  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101683710  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101681650  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101676567  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101684443  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101687213  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101679776  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101687324  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101676895  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101671137  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:2.7.11.25]
101688261  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101692999  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101687290  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
101689456  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
101677714  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
101678858  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
101688002  tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
101671650  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101686724  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101691050  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
101678623  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X14 [KO:K04354]
101685731  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
101679750  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
101686428  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
101670169  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
101670213  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
101677056  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
101678665  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X6 [KO:K11584]
101673249  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
101679697  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101671266  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101677587  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101676377  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
101674110  IL2; interleukin-2 [KO:K05429]
101686417  IL4; interleukin-4 [KO:K05430]
101688037  IL5; interleukin-5 [KO:K05428]
101672145  IL10; interleukin-10 [KO:K05443]
101693741  IFNG; interferon gamma [KO:K04687]
106004834  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101687148  TNF; tumor necrosis factor isoform X1 [KO:K03156]
101673063  CDK4; cyclin-dependent kinase 4 isoform X1 [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
mpuf04010  MAPK signaling pathway
mpuf04020  Calcium signaling pathway
mpuf04064  NF-kappa B signaling pathway
mpuf04120  Ubiquitin mediated proteolysis
mpuf04151  PI3K-Akt signaling pathway
mpuf04514  Cell adhesion molecules
mpuf04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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