KEGG PATHWAY: ocu04660

PATHWAY: ocu04660

Entry

ocu04660                    Pathway

Name

T cell receptor signaling pathway - Oryctolagus cuniculus (rabbit)

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

ocu04660

T cell receptor signaling pathway

Other DBs

GO:

0050852

Organism

Oryctolagus cuniculus (rabbit) [GN:ocu]

Gene

100008602

IFNG; interferon gamma precursor [KO:K04687]

100008616

CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]

100008617

CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]

100008701

IL10; interleukin-10 precursor [KO:K05443]

100008856

JUN; transcription factor Jun [KO:K04448]

100008859

[KO:K17333]

100008965

[KO:K04393]

100008998

CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]

100009039

[KO:K02089] [EC:2.7.11.22]

100009088

TNF; tumor necrosis factor precursor [KO:K03156]

100009139

PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]

100009152

CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]

100009215

PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]

100009216

PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]

100009252

PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]

100009300

PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]

100009316

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

100009412

CTLA4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]

100009423

PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]

100009434

[KO:K11584]

100009487

PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]

100009533

PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]

100009535

PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]

100302454

IL4; interleukin-4 isoform 1 precursor [KO:K05430]

100302458

IL2; interleukin-2 isoform 1 precursor [KO:K05429]

100328616

PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]

100328617

PPP2R2C; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]

100328720

CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]

100328905

IKBKG; NF-kappa-B essential modulator [KO:K07210]

100337822

[KO:K00922] [EC:2.7.1.153]

100337999

[KO:K04440] [EC:2.7.11.24]

100338345

[KO:K04379]

100339253

[KO:K12076]

100339465

[KO:K07361]

100339517

[KO:K07293] [EC:3.1.3.48]

100339529

[KO:K06451]

100339741

[KO:K05703] [EC:2.7.10.2]

100340322

[KO:K07369] [EC:3.4.22.-]

100340661

[KO:K04513]

100340742

[KO:K05736] [EC:2.7.11.1]

100341627

[KO:K05730]

100341695

[KO:K04441] [EC:2.7.11.24]

100341923

[KO:K07364] [EC:2.7.10.2]

100341934

[KO:K05734] [EC:2.7.11.1]

100342021

[KO:K07360] [EC:2.7.10.2]

100342500

[KO:K04364]

100342664

[KO:K04440] [EC:2.7.11.24]

100342852

[KO:K04456] [EC:2.7.11.1]

100343368

[KO:K04513]

100343571

[KO:K04427] [EC:2.7.11.25]

100343680

[KO:K04513]

100343779

[KO:K06744]

100344161

[KO:K04441] [EC:2.7.11.24]

100344241

[KO:K07828]

100344482

[KO:K04393]

100344533

[KO:K06268]

100345181

[KO:K00922] [EC:2.7.1.153]

100345250

[KO:K02649]

100346391

[KO:K03099]

100346856

[KO:K04513]

100346929

[KO:K04440] [EC:2.7.11.24]

100346997

[KO:K11584]

100347273

[KO:K05733] [EC:2.7.11.1]

100347345

[KO:K04371] [EC:2.7.11.24]

100347407

[KO:K04366] [EC:2.7.11.1]

100347487

[KO:K07827]

100347954

[KO:K06276] [EC:2.7.11.1]

100348286

[KO:K04354]

100348561

[KO:K04371] [EC:2.7.11.24]

100348648

[KO:K05697] [EC:3.1.3.48]

100348663

[KO:K00922] [EC:2.7.1.153]

100348842

[KO:K03083] [EC:2.7.11.26]

100348921

[KO:K05735] [EC:2.7.11.1]

100348967

[KO:K04513]

100349102

[KO:K05856] [EC:2.7.10.2]

100349426

[KO:K02580]

100349958

[KO:K01116] [EC:3.1.4.11]

100350076

[KO:K07362]

100350614

[KO:K04441] [EC:2.7.11.24]

100351032

[KO:K04466] [EC:2.7.11.25]

100351986

[KO:K07363] [EC:2.7.10.2]

100352056

[KO:K04409] [EC:2.7.11.1]

100352250

[KO:K06713]

100352378

[KO:K04446]

100352809

[KO:K06452]

100353545

[KO:K11583]

100353706

[KO:K04456] [EC:2.7.11.1]

100353755

[KO:K19862]

100353824

[KO:K17332]

100354145

[KO:K07367]

100355092

[KO:K03456]

100355159

[KO:K11583]

100355340

[KO:K06452]

100355469

[KO:K22517] [EC:2.3.2.27]

100355566

[KO:K04415] [EC:2.7.11.25]

100355758

[KO:K03456]

100355767

[KO:K06459]

100355876

[KO:K07368]

100355888

[KO:K04467] [EC:2.7.11.10]

100356153

[KO:K06450]

100356245

[KO:K04348] [EC:3.1.3.16]

100356250

[KO:K04513]

100356269

[KO:K06458]

100356401

[KO:K07209] [EC:2.7.11.10]

100356580

[KO:K11583]

100356615

[KO:K03099]

100357341

[KO:K04734]

100357841

[KO:K02649]

100358075

[KO:K05428]

100358388

CD40LG; CD40 ligand [KO:K03161]

100358703

[KO:K07365]

100358807

[KO:K06478] [EC:3.1.3.48]

100359054

[KO:K05872]

100359283

[KO:K02581]

100359319

[KO:K04350]

103345313

[KO:K04431] [EC:2.7.12.2]

103346035

[KO:K04441] [EC:2.7.11.24]

103350889

[KO:K18052] [EC:2.7.11.13]

103352473

[KO:K07366]

108178285

[KO:K10784]

127485184

[KO:K04735]

127486116

[KO:K04456] [EC:2.7.11.1]

127486605

[KO:K02833]

127489236

[KO:K07827]

127489461

[KO:K04368] [EC:2.7.12.2]

127489660

[KO:K04513]

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

ocu04010

MAPK signaling pathway

ocu04020

Calcium signaling pathway

ocu04064

NF-kappa B signaling pathway

ocu04120

Ubiquitin mediated proteolysis

ocu04151