KEGG   PATHWAY: biu04660
biu04660                    Pathway                                

T cell receptor signaling pathway - Bos indicus (zebu cattle)
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.
Organismal Systems; Immune system
Pathway map
biu04660  T cell receptor signaling pathway

Other DBs
GO: 0050852
Bos indicus (zebu cattle) [GN:biu]
109569960  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
109569940  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
109569992  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
109577671  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
109558922  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
109566151  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
109566150  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
109570498  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:]
109572368  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:]
109563811  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:]
109565800  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:]
109574975  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
109578681  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
109562249  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:]
109560451  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:]
109560012  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
109566126  NCK2; cytoplasmic protein NCK2 [KO:K19862]
109565687  VAV2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730]
109560955  VAV1; proto-oncogene vav [KO:K05730]
109556793  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
109559835  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
109574040  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
109554525  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:]
109555415  PAK3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:]
109567943  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:]
109564925  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:]
109576171  RHOA; transforming protein RhoA [KO:K04513]
109574100  CDC42; cell division control protein 42 homolog [KO:K04393]
109562672  DLG1; disks large homolog 1 [KO:K12076]
109577010  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
109577419  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
109567698  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:]
109563107  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:]
109553732  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:]
109560300  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:]
109566227  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
109563306  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
109577750  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
109567554  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
109572084  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
109566002  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109564346  SOS2; son of sevenless homolog 2 [KO:K03099]
109564913  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
109570973  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
109565363  FOS; proto-oncogene c-Fos [KO:K04379]
109556235  JUN; transcription factor AP-1 [KO:K04448]
109567889  PRKCQ; protein kinase C theta type [KO:K18052] [EC:]
109578732  CARD11; caspase recruitment domain-containing protein 11 isoform X1 [KO:K07367]
109556122  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
109577685  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
109563902  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:]
109560948  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:]
109561331  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
109560650  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
109553773  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
109553086  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
109553353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:]
109560296  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
109554392  RELA; transcription factor p65 [KO:K04735]
109575581  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109572576  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
109577350  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
109569809  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
109569829  ICOS; inducible T-cell costimulator [KO:K06713]
109555532  CD40LG; CD40 ligand [KO:K03161]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
109578066  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
109568007  MAP3K8; mitogen-activated protein kinase kinase kinase 8 isoform X1 [KO:K04415] [EC:]
109574056  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
109556613  PDCD1; programmed cell death protein 1 isoform X1 [KO:K06744]
109569818  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
109558908  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:]
109568926  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:]
109571028  IL2; interleukin-2 [KO:K05429]
109561213  IL4; interleukin-4 [KO:K05430]
109561216  IL5; interleukin-5 [KO:K05428]
109570808  IL10; interleukin-10 [KO:K05443]
109558719  IFNG; interferon gamma [KO:K04687]
109561218  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
109577428  TNF; tumor necrosis factor [KO:K03156]
109559308  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Chen L.
Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity.
Nat Rev Immunol 4:336-47 (2004)
Macian F.
NFAT proteins: key regulators of T-cell development and function.
Nat Rev Immunol 5:472-84 (2005)
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Tec family kinases in T lymphocyte development and function.
Annu Rev Immunol 23:549-600 (2005)
Huang Y, Wange RL.
T cell receptor signaling: beyond complex complexes.
J Biol Chem 279:28827-30 (2004)
Schmitz ML, Bacher S, Dienz O.
NF-kappaB activation pathways induced by T cell costimulation.
FASEB J 17:2187-93 (2003)
Alegre ML, Frauwirth KA, Thompson CB.
T-cell regulation by CD28 and CTLA-4.
Nat Rev Immunol 1:220-8 (2001)
Horejsi V, Zhang W, Schraven B.
Transmembrane adaptor proteins: organizers of immunoreceptor signalling.
Nat Rev Immunol 4:603-16 (2004)
Baniyash M.
TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response.
Nat Rev Immunol 4:675-87 (2004)
Sechi AS, Wehland J.
Interplay between TCR signalling and actin cytoskeleton dynamics.
Trends Immunol 25:257-65 (2004)
Okkenhaug K, Vanhaesebroeck B.
PI3K in lymphocyte development, differentiation and activation.
Nat Rev Immunol 3:317-30 (2003)
Palacios EH, Weiss A.
Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
Oncogene 23:7990-8000 (2004)
Kane LP, Lin J, Weiss A.
It's all Rel-ative: NF-kappaB and CD28 costimulation of T-cell activation.
Trends Immunol 23:413-20 (2002)
Acuto O, Michel F.
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Nat Rev Immunol 3:939-51 (2003)
Finkelstein LD, Schwartzberg PL.
Tec kinases: shaping T-cell activation through actin.
Trends Cell Biol 14:443-51 (2004)
Duan L, Reddi AL, Ghosh A, Dimri M, Band H.
The Cbl family and other ubiquitin ligases: destructive forces in control of antigen receptor signaling.
Immunity 21:7-17 (2004)
Schrum AG, Turka LA, Palmer E.
Surface T-cell antigen receptor expression and availability for long-term antigenic signaling.
Immunol Rev 196:7-24 (2003)
Smith-Garvin JE, Koretzky GA, Jordan MS
T cell activation.
Annu Rev Immunol 27:591-619 (2009)
Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, Crabtree GR, Brown PO
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
Proc Natl Acad Sci U S A 99:11796-801 (2002)
Blonska M, Lin X
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes.
Immunol Rev 228:199-211 (2009)
Rebeaud F, Hailfinger S, Thome M
Dlgh1 and Carma1 MAGUK proteins contribute to signal specificity downstream of TCR activation.
Trends Immunol 28:196-200 (2007)
Ashwell JD
The many paths to p38 mitogen-activated protein kinase activation in the immune system.
Nat Rev Immunol 6:532-40 (2006)
Round JL, Humphries LA, Tomassian T, Mittelstadt P, Zhang M, Miceli MC
Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors.
Nat Immunol 8:154-61 (2007)
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
biu04064  NF-kappa B signaling pathway
biu04120  Ubiquitin mediated proteolysis
biu04151  PI3K-Akt signaling pathway
biu04514  Cell adhesion molecules
biu04810  Regulation of actin cytoskeleton
KO pathway

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