KEGG PATHWAY: rno04660

PATHWAY: rno04660

Entry

rno04660 Pathway

Name

T cell receptor signaling pathway - Rattus norvegicus (rat)

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

rno04660

T cell receptor signaling pathway

Other DBs

BSID:

83472

GO:

0050852

Organism

Rattus norvegicus (rat) [GN:rno]

Gene

100911007	T-cell receptor beta chain T17T-22-like; K10785 T-cell receptor beta chain V region [KO:K10785]
100911086	T-cell receptor beta chain T17T-22-like; K10785 T-cell receptor beta chain V region [KO:K10785]
100912777	T-cell receptor beta chain T17T-22-like; K10785 T-cell receptor beta chain V region [KO:K10785]
25710	Cd3d; CD3 molecule, delta [KO:K06450]
315609	Cd3e; CD3 molecule, epsilon [KO:K06451]
300678	Cd3g; CD3 molecule, gamma [KO:K06452]
25300	Cd247; Cd247 molecule [KO:K06453]
24932	Cd4; Cd4 molecule [KO:K06454]
24930	Cd8a; CD8a molecule [KO:K06458]
24931	Cd8b; CD8b molecule [KO:K06459]
24699	Ptprc; protein tyrosine phosphatase, receptor type, C [KO:K06478] [EC:3.1.3.48]
313050	Lck; lymphocyte-specific protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
25150	Fyn; FYN oncogene related to SRC, FGR, YES [KO:K05703] [EC:2.7.10.2]
301348	Zap70; zeta-chain (TCR) associated protein kinase 70 [KO:K07360] [EC:2.7.10.2]
155918	Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
81511	Lat; linker for activation of T cells [KO:K07362]
363577	Itk; IL2-inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
84492	Tec; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
300955	Nck1; NCK adaptor protein 1 [KO:K07365]
316369	Nck2; NCK adaptor protein 2 [KO:K07365]
25156	Vav1; vav 1 guanine nucleotide exchange factor [KO:K05730]
295378	Vav3; vav 3 guanine nucleotide exchange factor [KO:K05730]
296603	Vav2; vav 2 guanine nucleotide exchange factor [KO:K05730]
366962	Grap2; GRB2-related adaptor protein 2 [KO:K07366]
81504	Grb2; growth factor receptor bound protein 2 [KO:K04364]
29431	Pak1; p21 protein (Cdc42/Rac)-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
29432	Pak2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
100910732	serine/threonine-protein kinase PAK 2-like; K04410 p21-activated kinase 2 [EC:2.7.11.1] [KO:K04410] [EC:2.7.11.1]
29433	Pak3; p21 protein (Cdc42/Rac)-activated kinase 3 [KO:K05733] [EC:2.7.11.1]
292756	Pak4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
296078	Pak6; p21 protein (Cdc42/Rac)-activated kinase 6 [KO:K05735] [EC:2.7.11.1]
311450	Pak7; p21 protein (Cdc42/Rac)-activated kinase 7 [KO:K05736] [EC:2.7.11.1]
117273	Rhoa; ras homolog family member A [KO:K04513]
297173	RSA-14-44; RSA-14-44 protein [KO:K04513]
64465	Cdc42; cell division cycle 42 (GTP binding protein) [KO:K04393]
25252	Dlg1; discs, large homolog 1 (Drosophila) [KO:K12076]
81649	Mapk14; mitogen activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352	Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513	Mapk13; mitogen activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314	Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25738	Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
24674	Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
24675	Ppp3cb; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
171378	Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
29748	Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
29749	Ppp3r2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
64152	Chp; calcium binding protein p22 [KO:K06268]
500462	RGD1564956; similar to calcium binding protein P22 [KO:K06268]
499969	RGD1565588; similar to calcium binding protein P22 [KO:K06268]
308965	Chp2; calcineurin-like EF hand protein 2 [KO:K06268]
305897	Nfatc4; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [KO:K04446]
307820	Nfat5; nuclear factor of activated T-cells 5, tonicity-responsive [KO:K04446]
311658	Nfatc2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K04446]
361400	Nfatc3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K04446]
100361818	Nfatc1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
85384	Sos2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
313845	Sos1; Son of sevenless homolog 1 (Drosophila) [KO:K03099]
29434	Rasgrp1; RAS guanyl releasing protein 1 (calcium and DAG-regulated) [KO:K04350]
293621	Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
24525	Kras; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
24605	Nras; neuroblastoma ras oncogene [KO:K07828]
24703	Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
170851	Map2k1; mitogen activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960	Map2k2; mitogen activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590	Mapk1; mitogen activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689	Mapk3; mitogen activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
314322	Fos; FBJ osteosarcoma oncogene [KO:K04379]
24516	Jun; jun proto-oncogene [KO:K04448]
100363332	caspase recruitment domain family; K07367 caspase recruitment domain-containing protein 11 [KO:K07367]
83477	Bcl10; B-cell CLL/lymphoma 10 [KO:K07368]
307366	Malt1; mucosa associated lymphoid tissue lymphoma translocation gene 1 [KO:K07369] [EC:3.4.22.-]
313121	Map3k7; mitogen activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100910771	mitogen-activated protein kinase kinase kinase 7-like; K04427 mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] [KO:K04427] [EC:2.7.11.25]
363855	Map2k7; mitogen activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
309361	Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
84351	Ikbkb; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
309295	Ikbkg; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
81736	Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
309165	Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
25493	Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
81525	Nfkbib; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
316241	Nfkbie; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon [KO:K05872]
25660	Cd28; Cd28 molecule [KO:K06470]
64545	Icos; inducible T-cell co-stimulator [KO:K06713]
84349	Cd40lg; CD40 ligand [KO:K03161]
25513	Pik3r1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
60664	Pik3r3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
29741	Pik3r2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
497931	Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
85243	Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
170911	Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
366508	Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
298947	Pik3cg; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
116551	Pdk1; pyruvate dehydrogenase kinase, isozyme 1 [KO:K12077] [EC:2.7.11.2]
24185	Akt1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
25233	Akt2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
29414	Akt3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
116596	Map3k8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
360640	Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
84027	Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
301626	Pdcd1; programmed cell death 1 [KO:K06744]
100911478	programmed cell death protein 1-like; K06744 programmed cell death protein 1 [KO:K06744]
63835	Ctla4; cytotoxic T-lymphocyte-associated protein 4 [KO:K06538]
116689	Ptpn6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
292699	Cblc; Cbl proto-oncogene, E3 ubiquitin protein ligase C [KO:K04707] [EC:6.3.2.19]
171136	Cblb; Cbl proto-oncogene, E3 ubiquitin protein ligase B [KO:K04707] [EC:6.3.2.19]
500985	Cbl; Cbl proto-oncogene, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
116562	Il2; interleukin 2 [KO:K05429]
287287	Il4; interleukin 4 [KO:K05430]
24497	Il5; interleukin 5 [KO:K05428]
25325	Il10; interleukin 10 [KO:K05443]
25712	Ifng; interferon gamma [KO:K04687]
116630	Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
24835	Tnf; tumor necrosis factor [KO:K03156]
94201	Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
50658	Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]

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)

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)

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)

Reference

PMID:15084594

Authors

Huang Y, Wange RL.

Title

T cell receptor signaling: beyond complex complexes.

Journal

J Biol Chem 279:28827-30 (2004)

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)

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)

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)

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)

Reference

PMID:15099566

Authors

Sechi AS, Wehland J.

Title

Interplay between TCR signalling and actin cytoskeleton dynamics.

Journal

Trends Immunol 25:257-65 (2004)

Reference

PMID:12669022

Authors

Okkenhaug K, Vanhaesebroeck B.

Title

PI3K in lymphocyte development, differentiation and activation.

Journal

Nat Rev Immunol 3:317-30 (2003)

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)

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)

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)

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)

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)

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)

Reference

PMID:19132916

Authors

Smith-Garvin JE, Koretzky GA, Jordan MS

Title

T Cell Activation.

Journal

Annu Rev Immunol (2009)

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)

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)

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)

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)

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)

KO pathway

ko04660

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Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (116)   
   KEGG GENES (116)   
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