TCR signaling (Homo sapiens)

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517, 12, 272, 2924, 32, 46, 47181621, 3912, 2729, 3025, 453543142921, 391913131, 433011261020, 33, 3623, 344, 6, 109, 37, 381, 2821, 398, 415, 29, 301044, 483, 151712, 271144811, 224219cytosolp-SLP-76:ADAPBcl10ADPPhosphatidylinositol-4,5-bisphosphateK63-polyubiquitinADPTAB2/TAK1 complexATPTAK1/TAB2 complex bound to TRAF6/CBM complexADPActivated CARMA1ZAP-70 bound to phosphorylated ITAM motifsIKK complexpyrophosphateTRAF6ADPphopshorylated PLC-gamma1 bound to SLP-76Active PKC theta bound to DAGH2OZAP-70p-SLP-76:NCK1:WASPADPATPATPphospho tyrosine ZAP-70ADPATPCsk:p-PAGTRAF6 trimer bound to CBM complexActivated PLC gamma1 bound to PIP2IKK complex with phosphorylated IKK betaBcl10 trimer bound to CARMA1 trimerAntigen-bearing MHC Class II :TCR complex:CD4: Lck phosphorylated at Tyr394Antigen-bearing MHC Class II : TCR complex:CD4:LckLAT with phospho TBSMsPI3K bound to TRATPTEN (Mg2+ cofactor)ZAP-70 and ITK tyrosine kinasesPIP3, PI(3,4)P2ATPBcl10 bound to CARMA1ATPPKC theta (opened conformation) bound to DAGUbc13/Uev1A complexATPUbc13/Uev1A complexADPPLC-gamma1 bound to SLP-76:Gads:LATPhosphatidylinositol-3,4,5-trisphosphatePhospholipase C gamma 1p-SLP-76:NCK1PLC-gamma1 bound to LAT at pY312H2OLeukocyte common antigen precursorITKSLP-76Phosphorylated Bcl10 bound to CARMA1 and RIP2ATPIkB(alpha):NF-kB complexSHIP1NF-kB complexADAPPDK1 bound to either PIP3 or PI(3,4)P2Phospho-IkBAPhospho TRATADPdiacylglycerolsIKK complex with Ub-NEMOInactive PKC theta bound to DAGRIP2ATPPDK1CARMA1Ena/VASP proteinsPhosphorylated PLC-gamma1 bound to LAT or SLP-76PLC-gamma1 bound to LAT or SLP-76ADPNCK1p-SLP-76:NCK:PAK1D-myo-Inositol 1,4,5-trisphosphateK63-polyubiquitinADPp-SLP-76:ADAP:Ena/VASPATPADPATPATPPhospho-Phospholipase C gamma 1CARMA1 bound to PDK1phosphorylated PLC-gamma1 bound to LATAntigen-bearing MHC Class II : TCR complex:CD4:p-Lck(Y505)PI3KPhosphatidylinositol-4,5-bisphosphateATPPhosphorylated CARMA1inactive PKC theta (closed conformation)Gads bound to LAT at phosphotyrosineATPATPphosphorylated SLP-76:Gads: LATActivated ZAP-70MALT1 trimerLATphosphorylated Bcl10Tyrosine-protein kinase CSKGRB2-related adapter protein 2ADPSLP-76 bound to Gads:LATAntigen-bearing MHC Class II: TCR with phosphorylated ITAMs:CD4Antigen-bearing MHC Class II :TCR complex:CD4: Lck phosphorylated at Tyr394ADPADPATPp-PAG1OrthophosphatePI(3,4)P2ADPITK bound to SLP-76:Gads:LATPAKpyrophosphateUb-TRAF6 trimer bound to CBM complexPhosphatidylinositol-4,5-bisphosphatephosphorylated SLP-76MALT1 trimer bound to Bcl10 and CARMA1 trimerWASPADPdiacylglycerolsCARMA1 trimer40


Description

The TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen presenting cells (APCs) results in the activation of protein tyrosine kinases (PTKs) that associate with CD3 and TCR zeta subunits and the co-receptor CD4. Members of the Src kinases (Lck), Syk kinases (ZAP-70), Tec (Itk) and Csk families of nonreceptor PTKs play a crucial role in T cell activation. Activation of PTKs following TCR engagement results in the recruitment and tyrosine phosphorylation of enzymes such as phospholipase C gamma1 and Vav as well as critical adaptor proteins such as LAT, SLP-76 and Gads. These proximal activation leads to reorganization of the cytoskeleton as well as transcription activation of multiple genes leading to T lymphocyte proliferation, differentiation and/or effector function.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114986view16:51, 25 January 2021ReactomeTeamReactome version 75
113430view11:50, 2 November 2020ReactomeTeamReactome version 74
112632view16:01, 9 October 2020ReactomeTeamReactome version 73
101547view11:41, 1 November 2018ReactomeTeamreactome version 66
101082view21:24, 31 October 2018ReactomeTeamreactome version 65
100611view19:58, 31 October 2018ReactomeTeamreactome version 64
100162view16:43, 31 October 2018ReactomeTeamreactome version 63
99712view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93802view13:37, 16 August 2017ReactomeTeamreactome version 61
93340view11:20, 9 August 2017ReactomeTeamreactome version 61
86427view09:17, 11 July 2016ReactomeTeamreactome version 56
83133view10:06, 18 November 2015ReactomeTeamVersion54
81476view13:00, 21 August 2015ReactomeTeamVersion53
76950view08:22, 17 July 2014ReactomeTeamFixed remaining interactions
76655view12:02, 16 July 2014ReactomeTeamFixed remaining interactions
75984view10:04, 11 June 2014ReactomeTeamRe-fixing comment source
75687view11:02, 10 June 2014ReactomeTeamReactome 48 Update
75043view13:55, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74687view08:45, 30 April 2014ReactomeTeamReactome46
68930view17:33, 8 July 2013MaintBotUpdated to 2013 gpml schema
45094view21:15, 6 October 2011KhanspersOntology Term : 'T cell receptor signaling pathway' added !
42142view22:00, 4 March 2011MaintBotAutomatic update
39953view05:58, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1D-myo-Inositol

1,4,5-trisphosphate

Metabolite16595 (ChEBI)
ADAP ProteinO15117 (UniProt)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Activated CARMA1 ComplexREACT_13227 (Reactome)
Activated PLC

gamma1 bound to PIP2

ComplexREACT_13147 (Reactome)
Activated ZAP-70 ComplexREACT_13133 (Reactome)
Active PKC theta

bound to DAG

ComplexREACT_12934 (Reactome)
Antigen-bearing

MHC Class II  : TCR complex:CD4:Lck

ComplexREACT_13095 (Reactome)
Antigen-bearing

MHC Class II : TCR complex:CD4:p-Lck (Y505)

ComplexREACT_12773 (Reactome)
Antigen-bearing

MHC Class II :TCR complex:CD4: Lck phosphorylated at Tyr394

ComplexREACT_12817 (Reactome)
Antigen-bearing MHC

Class II: TCR with phosphorylated ITAMs:CD4

ComplexREACT_12725 (Reactome)
Bcl10 ProteinO95999 (UniProt)
Bcl10 bound to

CARMA1

ComplexREACT_13143 (Reactome) Bcl10 interacts with the oligomerized CARMA1 and this is mediated by the CARD-CARD domainn interaction.
Bcl10 trimer bound

to CARMA1 trimer

ComplexREACT_12824 (Reactome)
CARMA1 ProteinQ9BXL7 (UniProt)
CARMA1 bound to

PDK1

ComplexREACT_13330 (Reactome)
CARMA1 trimer ComplexREACT_13044 (Reactome)
Csk:p-PAG ComplexREACT_13273 (Reactome)
Ena/VASP proteins ProteinREACT_20983 (Reactome)
GRB2-related

adapter protein 2

ProteinO75791 (UniProt)
Gads bound to LAT

at phosphotyrosine

ComplexREACT_13309 (Reactome)
H2O Metabolite15377 (ChEBI)
IKK complex ComplexREACT_7693 (Reactome)
IKK complex with

Ub-NEMO

ComplexREACT_12853 (Reactome)
IKK complex with

phosphorylated IKK beta

ComplexREACT_13373 (Reactome)
ITK ProteinQ08881 (UniProt)
ITK bound to SLP-

76:Gads:LAT

ComplexREACT_13016 (Reactome)
IkB(alpha):NF-kB

complex

ComplexREACT_12767 (Reactome)
Inactive PKC theta

bound to DAG

ComplexREACT_13197 (Reactome)
K63-polyubiquitin REACT_21645 (Reactome)
LAT ProteinO43561 (UniProt)
LAT with phospho

TBSMs

ProteinO43561 (UniProt)
Leukocyte common

antigen precursor

ProteinP08575 (UniProt)
MALT1 trimer ComplexREACT_12682 (Reactome)
MALT1 trimer bound

to Bcl10 and CARMA1 trimer

ComplexREACT_13172 (Reactome)
NCK1 ProteinP16333 (UniProt)
NF-kB complex ComplexREACT_12832 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAK ProteinREACT_19640 (Reactome)
PDK1 ProteinO15530 (UniProt)
PDK1 bound to either

PIP3 or PI(3,4)P2

ComplexREACT_12991 (Reactome)
PI(3,4)P2 Metabolite16152 (ChEBI)
PI3K ComplexREACT_4240 (Reactome)
PI3K bound to TRAT ComplexREACT_13152 (Reactome)
PIP3, PI(3,4)P2 MetaboliteREACT_12804 (Reactome)
PKC theta (opened

conformation) bound to DAG

ComplexREACT_12758 (Reactome)
PLC-gamma1 bound

to LAT at pY312

ComplexREACT_13281 (Reactome)
PLC-gamma1 bound

to LAT or SLP-76

ComplexREACT_13341 (Reactome)
PLC-gamma1 bound

to SLP-76:Gads:LAT

ComplexREACT_13137 (Reactome)
PTEN (Mg2+

cofactor)

ComplexREACT_12877 (Reactome)
Phosphatidylinositol-

3,4,5-trisphosphate

Metabolite16618 (ChEBI)
Phosphatidylinositol-

4,5-bisphosphate

Metabolite18348 (ChEBI)
Phospho TRAT ProteinQ6PIZ9 (UniProt)
Phospho-

Phospholipase C gamma 1

ProteinP19174 (UniProt)
Phospho-IkBA ProteinP25963 (UniProt)
Phospholipase C

gamma 1

ProteinP19174 (UniProt)
Phosphorylated

Bcl10 bound to CARMA1 and RIP2

ComplexREACT_12759 (Reactome) Bcl10 interacts with the oligomerized CARMA1 and this is mediated by the CARD-CARD domainn interaction.
Phosphorylated

CARMA1

ProteinQ9BXL7 (UniProt)
Phosphorylated PLC-

gamma1 bound to LAT or SLP-76

ComplexREACT_13004 (Reactome)
RIP2 ProteinO43353 (UniProt)
SHIP1 ProteinQ92835 (UniProt)
SLP-76 ProteinQ13094 (UniProt)
SLP-76 bound to

Gads:LAT

ComplexREACT_13131 (Reactome)
TAB2/TAK1 complex ComplexREACT_13271 (Reactome)
TAK1/TAB2 complex

bound to TRAF6/CBM complex

ComplexREACT_12884 (Reactome)
TRAF6 ProteinQ9Y4K3 (UniProt)
TRAF6 trimer bound

to CBM complex

ComplexREACT_12970 (Reactome)
Tyrosine-protein

kinase CSK

ProteinP41240 (UniProt)
Ub-TRAF6 trimer

bound to CBM complex

ComplexREACT_12752 (Reactome)
Ubc13/Uev1A

complex

ComplexREACT_12995 (Reactome)
WASP ProteinP42768 (UniProt)
ZAP-70 ProteinP43403 (UniProt)
ZAP-70 and ITK

tyrosine kinases

REACT_12862 (Reactome)
ZAP-70 bound to

phosphorylated ITAM motifs

ComplexREACT_13388 (Reactome)
diacylglycerols Metabolite18035 (ChEBI)
inactive PKC theta

(closed conformation)

ProteinQ04759 (UniProt)
p-PAG1 ProteinQ9NWQ8 (UniProt)
p-SLP-76:ADAP ComplexREACT_20709 (Reactome)
p-SLP-76:ADAP:

Ena/VASP

ComplexREACT_20995 (Reactome)
p-SLP-76:NCK1 ComplexREACT_20974 (Reactome)
p-SLP-76:NCK1:

WASP

ComplexREACT_21025 (Reactome)
p-SLP-76:NCK:PAK ComplexREACT_21232 (Reactome)
phopshorylated PLC-

gamma1 bound to SLP-76

ComplexREACT_13258 (Reactome)
phospho tyrosine

ZAP-70

ComplexREACT_13031 (Reactome)
phosphorylated

Bcl10

ProteinO95999 (UniProt)
phosphorylated PLC-

gamma1 bound to LAT

ComplexREACT_13372 (Reactome)
phosphorylated SLP-

76

ProteinQ13094 (UniProt)
phosphorylated SLP-

76:Gads: LAT

ComplexREACT_13181 (Reactome)
pyrophosphate Metabolite29888 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1927"
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