KEGG PATHWAY: mdo04660

PATHWAY: mdo04660

Entry

mdo04660 Pathway

Name

T cell receptor signaling pathway - Monodelphis domestica (opossum)

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

mdo04660

T cell receptor signaling pathway

Other DBs

BSID:

87181

GO:

0050852

Organism

Monodelphis domestica (opossum) [GN:mdo]

Gene

100618594	uncharacterized LOC100618594; K10784 T cell receptor alpha chain V region [KO:K10784]
100010040	TRB; t-cell receptor beta chain T17T-22-like [KO:K10785]
100617727	uncharacterized LOC100617727; K10785 T-cell receptor beta chain V region [KO:K10785]
100031472	t-cell surface glycoprotein CD3 delta chain-like; K06450 T-cell surface glycoprotein CD3 delta chain [KO:K06450]
100031478	t-cell surface glycoprotein CD3 epsilon chain-like; K06451 T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
100031464	t-cell surface glycoprotein CD3 gamma chain-like; K06452 T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
100017987	t-cell surface glycoprotein CD3 zeta chain-like; K06453 CD3Z antigen, zeta polypeptide [KO:K06453]
100016045	CD4; CD4 molecule [KO:K06454]
100029709	CD8A; CD8a molecule [KO:K06458]
100272160	CD8B; CD8b molecule [KO:K06459]
100026890	PTPRC; protein tyrosine phosphatase, receptor type, C [KO:K06478] [EC:3.1.3.48]
100025680	tyrosine-protein kinase Lck-like; K05856 lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2] [KO:K05856] [EC:2.7.10.2]
100022459	FYN; FYN oncogene related to SRC, FGR, YES [KO:K05703] [EC:2.7.10.2]
100025187	ZAP70; zeta-chain (TCR) associated protein kinase 70kDa [KO:K07360] [EC:2.7.10.2]
100026299	LCP2; lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) [KO:K07361]
100030005	ITK; IL2-inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
100019245	TEC; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
100016740	NCK1; NCK adaptor protein 1 [KO:K07365]
100014693	NCK2; NCK adaptor protein 2 [KO:K07365]
100029844	VAV3; vav 3 guanine nucleotide exchange factor [KO:K05730]
100015350	VAV2; vav 2 guanine nucleotide exchange factor [KO:K05730]
100020150	VAV1; vav 1 guanine nucleotide exchange factor [KO:K05730]
100011047	GRB2-related adapter protein 2-like; K07366 GRB2-related adaptor protein 2 [KO:K07366]
100022894	growth factor receptor-bound protein 2-like; K04364 growth factor receptor-binding protein 2 [KO:K04364]
100018336	serine/threonine-protein kinase PAK 1-like; K04409 p21-activated kinase 1 [EC:2.7.11.1] [KO:K04409] [EC:2.7.11.1]
100015796	PAK2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
100012727	serine/threonine-protein kinase PAK 3-like; K05733 p21-activated kinase 3 [EC:2.7.11.1] [KO:K05733] [EC:2.7.11.1]
100013977	PAK4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
100033279	serine/threonine-protein kinase PAK 7-like; K05736 p21-activated kinase 7 [EC:2.7.11.1] [KO:K05736] [EC:2.7.11.1]
100021110	transforming protein RhoA-like; K04513 Ras homolog gene family, member A [KO:K04513]
100012776	transforming protein RhoA-like; K04513 Ras homolog gene family, member A [KO:K04513]
100020086	transforming protein RhoA-like; K04513 Ras homolog gene family, member A [KO:K04513]
100023099	cell division control protein 42 homolog; K04393 cell division control protein 42 [KO:K04393]
100009767	cell division control protein 42 homolog; K04393 cell division control protein 42 [KO:K04393]
100012700	cell division control protein 42 homolog; K04393 cell division control protein 42 [KO:K04393]
100017371	DLG1; discs, large homolog 1 (Drosophila) [KO:K12076]
100010279	mitogen-activated protein kinase 12-like; K04441 p38 MAP kinase [EC:2.7.11.24] [KO:K04441] [EC:2.7.11.24]
100010891	mitogen-activated protein kinase 11-like; K04441 p38 MAP kinase [EC:2.7.11.24] [KO:K04441] [EC:2.7.11.24]
100026324	MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100028821	mitogen-activated protein kinase 13-like; K04441 p38 MAP kinase [EC:2.7.11.24] [KO:K04441] [EC:2.7.11.24]
100032696	PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
100014900	PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
100011077	PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
100033104	PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
100027667	calcium-binding protein p22-like; K06268 protein phosphatase 3, regulatory subunit [KO:K06268]
100033302	calcineurin subunit B type 1-like; K06268 protein phosphatase 3, regulatory subunit [KO:K06268]
100025432	NFATC4; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [KO:K04446]
100028106	NFAT5; nuclear factor of activated T-cells 5, tonicity-responsive [KO:K04446]
100028435	nuclear factor of activated T-cells; K04446 nuclear factor of activated T-cells, cytoplasmic [KO:K04446]
100023153	NFATC1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
100021991	NFATC3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K04446]
100618058	son of sevenless homolog 1-like; K03099 son of sevenless [KO:K03099]
100029256	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
100031728	RASGRP1; RAS guanyl releasing protein 1 (calcium and DAG-regulated) [KO:K04350]
100032921	GTPase HRas-like; K02833 GTPase HRas [KO:K02833]
100009992	GTPase KRas-like; K07827 GTPase KRas [KO:K07827]
554186	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
554197	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
100015410	RAF proto-oncogene serine/threonine-protein kinase-like; K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04366] [EC:2.7.11.1]
100018410	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018044	dual specificity mitogen-activated protein kinase kinase 2-like; K04369 mitogen-activated protein kinase kinase 2 [EC:2.7.12.2] [KO:K04369] [EC:2.7.12.2]
100028096	mitogen-activated protein kinase 1-like; K04371 extracellular signal-regulated kinase 1/2 [EC:2.7.11.24] [KO:K04371] [EC:2.7.11.24]
100012916	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100018285	proto-oncogene c-Fos-like; K04379 proto-oncogene protein c-fos [KO:K04379]
100018774	transcription factor AP-1-like; K04448 transcription factor AP-1 [KO:K04448]
100012814	CARD11; caspase recruitment domain family, member 11 [KO:K07367]
100011950	b-cell lymphoma/leukemia 10-like; K07368 B-cell CLL/lymphoma 10 [KO:K07368]
100016169	MALT1; mucosa associated lymphoid tissue lymphoma translocation gene 1 [KO:K07369] [EC:3.4.22.-]
100019975	MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100026752	dual specificity mitogen-activated protein kinase kinase 7-like; K04431 mitogen-activated protein kinase kinase 7 [EC:2.7.12.2] [KO:K04431] [EC:2.7.12.2]
100027952	CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100033031	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
100022918	NF-kappa-B essential modulator-like; K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma [KO:K07210]
100014446	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
100030053	transcription factor p65-like; K04735 transcription factor p65 [KO:K04735]
100011769	NF-kappa-B inhibitor alpha-like; K04734 NF-kappa-B inhibitor alpha [KO:K04734]
100013691	NF-kappa-B inhibitor beta-like; K02581 NF-kappa-B inhibitor beta [KO:K02581]
100013226	NF-kappa-B inhibitor epsilon-like; K05872 NF-kappa-B inhibitor epsilon [KO:K05872]
100017932	t-cell-specific surface glycoprotein CD28-like; K06470 CD28 antigen [KO:K06470]
100010217	CD40 ligand-like; K03161 tumor necrosis factor ligand superfamily member 5 [KO:K03161]
100019317	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
100012464	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
100032726	phosphatidylinositol 3-kinase regulatory subunit beta-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO:K02649]
100009879	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100010412	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100017332	phosphatidylinositol-4; K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153] [KO:K00922] [EC:2.7.1.153]
100027741	PDK1; pyruvate dehydrogenase kinase, isozyme 1 pseudogene [KO:K12077] [EC:2.7.11.2]
100014564	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
100019947	RAC-alpha serine/threonine-protein kinase-like; K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04456] [EC:2.7.11.1]
100027373	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
100018684	MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
100020668	MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100012447	GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100017900	cytotoxic T-lymphocyte protein 4-like; K06538 cytotoxic T-lymphocyte-associated protein 4 [KO:K06538]
100016514	PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
100031184	e3 ubiquitin-protein ligase CBL-like; K04707 E3 ubiquitin-protein ligase CBL [EC:6.3.2.19] [KO:K04707] [EC:6.3.2.19]
100023698	signal transduction protein CBL-C-like; K04707 E3 ubiquitin-protein ligase CBL [EC:6.3.2.19] [KO:K04707] [EC:6.3.2.19]
100011932	CBLB; Cbl proto-oncogene, E3 ubiquitin protein ligase B [KO:K04707] [EC:6.3.2.19]
100619184	interleukin-2-like; K05429 interleukin 2 [KO:K05429]
100617451	interleukin-4-like; K05430 interleukin 4 [KO:K05430]
100018747	interleukin-5-like; K05428 interleukin 5 [KO:K05428]
100616748	interleukin-10-like; K05443 interleukin 10 [KO:K05443]
100023069	tumor necrosis factor-like; K03156 tumor necrosis factor superfamily, member 2 [KO:K03156]

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 (103)   
   KEGG GENES (103)   
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