KEGG   PATHWAY: dro04660
dro04660                    Pathway                                

T cell receptor signaling pathway - Desmodus rotundus (common vampire bat)
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
dro04660  T cell receptor signaling pathway

Other DBs
GO: 0050852
Desmodus rotundus (common vampire bat) [GN:dro]
112314228  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
112314382  CD3E; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
112314387  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
112321742  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
112322003  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
112302983  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
112302981  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
112318902  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:]
112299317  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:]
112297021  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:]
112315209  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:]
112319500  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
112304844  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
112319647  ITK; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:]
112316881  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:]
112309536  NCK1; cytoplasmic protein NCK1 isoform X1 [KO:K07365]
112315145  NCK2; cytoplasmic protein NCK2 isoform X1 [KO:K19862]
112313799  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
112312402  VAV1; proto-oncogene vav [KO:K05730]
112306573  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
112321921  GRAP2; GRB2-related adapter protein 2 [KO:K07366]
112298645  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112316047  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:]
112320635  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:]
112296895  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:]
112320090  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:]
112303959  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:]
112311615  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:]
112309492  RHOA; transforming protein RhoA [KO:K04513]
112307557  transforming protein RhoA-like isoform X1 [KO:K04513]
112299195  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
112320513  DLG1; disks large homolog 1 isoform X1 [KO:K12076]
112302047  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
112321896  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
112302140  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
112322057  mitogen-activated protein kinase 11-like [KO:K04441] [EC:]
112303845  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:]
112305449  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:]
112317863  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:]
112305248  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:]
112297858  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
112304508  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
112322654  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
112303992  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
112300806  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
112297971  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112310995  SOS2; son of sevenless homolog 2 [KO:K03099]
112311978  RASGRP1; RAS guanyl-releasing protein 1 isoform X1 [KO:K04350]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112304041  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
112313707  NRAS; GTPase NRas [KO:K07828]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
112311412  FOS; proto-oncogene c-Fos [KO:K04379]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112320743  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:]
112319699  CARD11; caspase recruitment domain-containing protein 11 [KO:K07367]
112309355  BCL10; B-cell lymphoma/leukemia 10 [KO:K07368]
112322863  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [KO:K07369] [EC:3.4.22.-]
112296959  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:]
112305131  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
112300474  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:]
112321547  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:]
112296261  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
112317867  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112317202  RELA; transcription factor p65 [KO:K04735]
112296519  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112320245  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
112302226  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
112307972  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
112307652  ICOS; inducible T-cell costimulator [KO:K06713]
112307303  CD40LG; CD40 ligand isoform X1 [KO:K03161]
112321016  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112305224  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
112314466  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
112310002  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
112299448  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
112307667  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
112298319  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:]
112311458  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
112318919  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
112320130  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
112316842  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:]
112298609  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:]
112320540  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
112308039  PDCD1; programmed cell death protein 1 [KO:K06744]
112307993  CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
112321823  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:]
112320522  CBLB; E3 ubiquitin-protein ligase CBL-B isoform X1 [KO:K22517] [EC:]
112312503  IL2; interleukin-2 [KO:K05429]
112318159  IL4; interleukin-4 [KO:K05430]
112318060  IL5; LOW QUALITY PROTEIN: interleukin-5 [KO:K05428]
112315005  IL10; interleukin-10 [KO:K05443]
112319176  IFNG; interferon gamma [KO:K04687]
112301620  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
112302067  TNF; tumor necrosis factor isoform X1 [KO:K03156]
112319119  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)
dro04010  MAPK signaling pathway
dro04020  Calcium signaling pathway
dro04064  NF-kappa B signaling pathway
dro04120  Ubiquitin mediated proteolysis
dro04151  PI3K-Akt signaling pathway
dro04514  Cell adhesion molecules
dro04810  Regulation of actin cytoskeleton
KO pathway

DBGET integrated database retrieval system