KEGG   PATHWAY: vpc04660
Entry
vpc04660                    Pathway                                
Name
T cell receptor signaling pathway - Vicugna pacos (alpaca)
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
vpc04660  T cell receptor signaling pathway
vpc04660

Other DBs
GO: 0050852
Organism
Vicugna pacos (alpaca) [GN:vpc]
Gene
116278047  uncharacterized protein LOC116278047 [KO:K10784]
116280840  LOW QUALITY PROTEIN: uncharacterized protein LOC116280840 [KO:K10784]
102533755  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
102542709  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
102542471  CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
102539187  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
102530125  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
102525677  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
102525925  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
102533613  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X2 [KO:K06478] [EC:3.1.3.48]
102530493  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
102538350  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
102535826  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
102542276  LCP2; lymphocyte cytosolic protein 2 isoform X2 [KO:K07361]
102535219  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
102540749  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:2.7.10.2]
102543761  TEC; tyrosine-protein kinase Tec isoform X3 [KO:K07364] [EC:2.7.10.2]
102535963  NCK1; cytoplasmic protein NCK1 isoform X2 [KO:K07365]
102539556  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
102526475  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
102544949  VAV1; proto-oncogene vav [KO:K05730]
102532612  GRAP2; GRB2-related adapter protein 2 isoform X1 [KO:K07366]
102532895  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102543166  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102537616  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
102544290  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
102530768  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
102531142  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
102540697  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
102534196  RHOA; transforming protein RhoA [KO:K04513]
102530757  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102538971  DLG1; disks large homolog 1 isoform X3 [KO:K12076]
102525219  MAPK12; mitogen-activated protein kinase 12 isoform X7 [KO:K04441] [EC:2.7.11.24]
102531650  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102540698  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102541290  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102542680  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102540381  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X3 [KO:K04348] [EC:3.1.3.16]
102525703  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102543544  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
102538751  calcineurin subunit B type 2 [KO:K06268]
102543250  NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102541219  nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
102529936  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
102541429  SOS2; son of sevenless homolog 2 [KO:K03099]
102543818  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102538823  RASGRP1; LOW QUALITY PROTEIN: RAS guanyl-releasing protein 1 [KO:K04350]
102525363  HRAS; GTPase HRas isoform X1 [KO:K02833]
102529990  KRAS; GTPase KRas isoform X2 [KO:K07827]
102534785  NRAS; GTPase NRas [KO:K07828]
102543308  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102530118  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102534668  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102536713  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102528720  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102533186  FOS; proto-oncogene c-Fos [KO:K04379]
102541687  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102535606  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
102535767  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
102546072  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
102539824  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 isoform X1 [KO:K07369] [EC:3.4.22.-]
102534059  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102525041  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102528221  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102543430  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102539859  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102534431  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102528824  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102541871  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102532161  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102540197  RELA; transcription factor p65 isoform X1 [KO:K04735]
102524630  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102531744  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
102533893  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102526286  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
102542222  ICOS; inducible T-cell costimulator [KO:K06713]
102531240  CD40LG; CD40 ligand [KO:K03161]
102532395  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102536302  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102536225  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102540289  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102524821  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102543068  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102528174  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102526860  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102546009  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102542031  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102533792  MAP3K8; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102526769  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102539918  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102544423  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
102526544  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
102533120  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
102529754  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X3 [KO:K07293] [EC:3.1.3.48]
102539029  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
102536954  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102537087  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102545534  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102543888  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
102538057  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X2 [KO:K04354]
102544198  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
102531046  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X2 [KO:K04354]
102534388  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X3 [KO:K11583]
102540251  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
102542819  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
102544732  PPP2R5B; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
102528266  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
102527762  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X2 [KO:K11584]
102530318  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102541861  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
102527933  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:2.3.2.27]
102532988  IL2; interleukin-2 [KO:K05429]
102541329  IL4; interleukin-4 [KO:K05430]
102542408  IL5; interleukin-5 [KO:K05428]
102537608  IL10; interleukin-10 [KO:K05443]
102534412  IFNG; interferon gamma [KO:K04687]
102543825  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102541924  TNF; tumor necrosis factor [KO:K03156]
102532580  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
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
vpc04010  MAPK signaling pathway
vpc04020  Calcium signaling pathway
vpc04064  NF-kappa B signaling pathway
vpc04120  Ubiquitin mediated proteolysis
vpc04151  PI3K-Akt signaling pathway
vpc04514  Cell adhesion molecules
vpc04810  Regulation of actin cytoskeleton
KO pathway
ko04660   
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