Signaling by NTRK1 (Homo sapiens)

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1-422, 234431, 32528953293752464715-1733, 34243914362549, 50563018-205212102648453513741-432115, 165440145551382927, 281114clathrin-coated endocytic vesiclenucleoplasmendoplasmic reticulum lumencytosolGolgi lumenendosomePhosphatidylinositol-4,5-bisphosphateOrthophosphateRAL-GDPADPActive c-Src (p-Y419)PIP3:PDK1:Phospho-AKTPHLPP (Mn2+ cofactor)ERK5Phospho-MAP kinase p38 (Mg2+ cofactor)PIP3:RhoATrkA-1 receptorATPTORC2 complexActivated TrkA receptor:Phospho-IRS1/2H2OActivated TrkA receptor complexActivated TrkA receptor complexC-terminal modulator proteinDynein light chainC3GPhospho-AKTPhospho-MSK1RhoAIKKAphospho-CREBpyrophosphateActivated TrkA receptor complexActive AKTCalmodulin:CaMK IVAKTPhospho-SHCIntracellular Trk receptorTSC2-1CalmodulinATPAdenosine:Adenosine A2a receptorCalciumATPp21 RAS:GTPATPPACAP:PACAP type 1 receptorProtein Kinase A, catalytic subunitsFrs2AKT:CTMP:TRB3SRCOrthophosphateATPATPProline-rich AKT1 substrate 1Phospho-IKK1 (T23)MSK1ADPphospho-CREBPhospho-Forkhead box transcription factorOrthophosphate14-3-3 protein beta/alphaForkhead box transcription factorMAP kinase p38 (Mg2+ cofactor)ADPIP3 receptor:IP3 complexMAP kinase cascadeADPRap1-GDPGSK3ADPEndophilinADPCam-PDE 1 homodimerATPPTEN (Mg2+ cofactor)CREBPhospho-ELK1Active CalmodulinPhospho-TSC2-1ADPGDPGTPATPPKA catalytic subunitActivated TrkA receptor complexGTPRap1-GTPGRB2:SOS1GDPH2OActivated TrkA receptor complex:Phosphorylated Shc complexCalciumADPH2O1D-myo-Inositol 1,4,5-trisphosphateActivated TrkA receptor:IRS1/2Phospho-MAP kinase-activated protein kinase 2active Cam-PDE 1phospho-CREBADPActive Trk receptor complex:RIT/RIN-GTP:B-RAFPhospho-ERK1/2/5Activated TrkA receptor complexcAMP:PKA regulatory subunitp21 RAS:GTPRAL-GTPATPRap1-GDPATPPhospho-Cyclic-AMP-dependent transcription factor ATF-1GTPADPPhospho-Ribosomal protein S6 kinase 2GRK2ATPActive TrkA receptor:Frs2 complexATPATPADPActive TrkA receptor:Phospho-Frs2:CrkL:C3G complexPhospho-ERK5Guanine nucleotide exchange factorCrkL (SH3 domain)C3GActive TrkA receptor:Frs2 complexActivated TrkA receptor complex:Clathrin-coated vesicle:dynein:dynactin complexActivated TrkA receptor complex:Clathrin-coated vesicleCREBRAF activationATPbeta-NGF dimer:TrkA receptorCaMKIVPhospho-BAD protein (at S136)RAL-GDP3',5'-Cyclic AMPMAP kinase cascadePhospho-Phospholipase C gamma 1phospho-CREB dimerB-Raf (Zn2+ cofactor)Active Trk receptor complex:RIT/RIN-GTPActive TrkA receptor:Phospho-PLCG1 complexPIP3:PDK1:active AKTCDK inhibitordiacylglycerolsActive TrkA receptor complex:RIT/RIN-GDPDynamin-1/2/3Phosphatidylinositol-4,5-bisphosphateMAP kinase cascadeADPGDPPhospho-PKC-delta/epsilonGRB2:SOS:Phospho-SHCADPActivated TrkA receptor complex:Clathrin-coated vesicleADPPhospho-ERK dimerActivated TrkA receptor complex:Shc complexGDPIRS1/2Active TrkA receptor:Phospho-ARMS:Crk complexRas-GTP:RalGDS complexADPATPC-terminal modulator proteinPituitary adenylate cyclase activating polypeptide type I receptorCalmodulin:CaMK IVARMS:CrkActive TrkA receptor:Phospho-Frs2:CrkL complexActivated TrkA receptor complexATPPituitary adenylate cyclase activating polypeptide precursorOrthophosphateATPH2OMDM2Active TrkA receptor:Phospho-ARMS:Crk:C3G complexActive TrkA receptor:ARMS:Crk complexAMPADPADPPDK1:AKT:PIP3Phospho-MAP kinase p38 alpha/betaERK-specific DUSPActive TrkA:Phospho-ARMS:Crk:C3G:Rap1-GTP complexADPRalGDSPhospho-MEF2ADPPhospho-Proline-rich AKT1 substrate 1Phospho-GSK3p21 RAS:GDPActive TrkA receptor:Phospho-Frs2 complexGDPRibosomal protein S6 kinase 2Adenylate cyclase (Mg2+ cofactor)ATPPhospho-Caspase-9Cyclic-AMP-dependent transcription factor ATF-1ATPActive TrkA:Phospho-ARMS:Crk:C3G:Rap1:Phospho-B-Raf complexPhospho-IRS1/2:PI3K(p85:p110)adenosineB-Raf complexRIT/RIN-GDPMEF2Activated TrkA receptor:Phospho-IRS1/2:PI3K(p85:p110)BAD proteinShc transforming proteinbeta-NGF dimer:TrkA receptor dimerClathrin-coated vesiclePhospho-Orphan nuclear receptor NR4A1ELK1Tribbles homolog 3Active TrkA receptor:PLCG1 complexATPCREBATPB-Raf complexNR4A1_HumanADPADP3',5'-Cyclic AMPmature beta-NGF homodimerActive AKTPhospho-ERK5PI3KPhosphatidylinositol-4,5-bisphosphateOrthophosphatePhosphatidylinositol-3,4,5-trisphosphatePhospho-MDM2Phospho-Ribosomal protein S6 kinaseGTPPhospholipase C gamma 1H2ORibosomal protein S6 kinaseGDPRAF activationGTPADPphospho-CaMK IV:CalmodulinCalmodulinMEK5Intracellular Phosphorylated Trk receptorActive MAPKAP kinaseADPTribbles homolog 3GRK2:calmodulinADPPhospho-CDK inhibitorATPPDK1:AKTRap1-GTP:B-Raf complexMAPKAP kinaseCREBCaspase-9ATPGTPPhospho-STAT3ERK1/2/5H2OPKA tetramerSTAT3PP2A-ABdeltaC complexIP3 receptor homotetramerPKC-delta/epsilonATPActive AKTRap1-GTPAdenosine A2a receptorH2OATP556


Description

Trk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes is slower but long lasting. Signalling from the plasma membrane is annotated here. TRK signalling leads to proliferation in some cell types and neuronal differentiation in others. Proliferation is the likely outcome of short term signalling, as observed following stimulation of EGFR (EGF receptor). Long term signalling via TRK receptors, instead, was clearly shown to be required for neuronal differentiation in response to neurotrophins.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
123615view08:20, 7 August 2022EgonwModified title
115037view16:57, 25 January 2021ReactomeTeamReactome version 75
113481view11:55, 2 November 2020ReactomeTeamReactome version 74
112680view16:07, 9 October 2020ReactomeTeamReactome version 73
101597view11:46, 1 November 2018ReactomeTeamreactome version 66
101133view21:31, 31 October 2018ReactomeTeamreactome version 65
100661view20:05, 31 October 2018ReactomeTeamreactome version 64
100211view16:50, 31 October 2018ReactomeTeamreactome version 63
99762view15:16, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93968view13:48, 16 August 2017ReactomeTeamreactome version 61
93566view11:27, 9 August 2017ReactomeTeamreactome version 61
88055view13:48, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86668view09:23, 11 July 2016ReactomeTeamreactome version 56
83147view10:09, 18 November 2015ReactomeTeamVersion54
81496view13:02, 21 August 2015ReactomeTeamVersion53
76973view08:26, 17 July 2014ReactomeTeamFixed remaining interactions
76678view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76006view10:06, 11 June 2014ReactomeTeamRe-fixing comment source
75713view11:06, 10 June 2014ReactomeTeamReactome 48 Update
75066view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74710view08:47, 30 April 2014ReactomeTeamReactome46
69004view17:46, 8 July 2013MaintBotUpdated to 2013 gpml schema
42091view21:56, 4 March 2011MaintBotAutomatic update
39899view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
14-3-3

protein beta/alpha

ProteinP31946 (UniProt)
1D-myo-Inositol

1,4,5- trisphosphate

Metabolite16595 (ChEBI)
3',5'-Cyclic AMP Metabolite17489 (ChEBI)
ADP Metabolite16761 (ChEBI)
AKT ProteinREACT_13267 (Reactome)
AKT:CTMP:TRB3 ComplexREACT_12823 (Reactome)
AMP Metabolite16027 (ChEBI)
ARMS:Crk ComplexREACT_12089 (Reactome)
ATP Metabolite15422 (ChEBI)
Activated TrkA

receptor complex: Clathrin-coated vesicle

ComplexREACT_13141 (Reactome)
Activated TrkA

receptor complex: Clathrin-coated vesicle

ComplexREACT_13349 (Reactome)
Activated TrkA

receptor complex:Clathrin- coated vesicle: dynein:dynactin complex

ComplexREACT_13375 (Reactome)
Activated TrkA

receptor complex

ComplexREACT_10696 (Reactome)
Activated TrkA

receptor complex

ComplexREACT_10757 (Reactome)
Activated TrkA

receptor complex: Phosphorylated Shc complex

ComplexREACT_12114 (Reactome)
Activated TrkA

receptor complex:Shc complex

ComplexREACT_12103 (Reactome)
Activated TrkA

receptor:IRS1/2

ComplexREACT_13110 (Reactome)
Activated TrkA

receptor:Phospho- IRS1/2

ComplexREACT_13002 (Reactome)
Activated TrkA

receptor:Phospho- IRS1/2:PI3K(p85: p110)

ComplexREACT_12678 (Reactome)
Active AKT ProteinREACT_13116 (Reactome)
Active AKT ProteinREACT_13319 (Reactome)
Active AKT ProteinREACT_13332 (Reactome)
Active Calmodulin ComplexREACT_3178 (Reactome)
Active MAPKAP kinase ProteinREACT_12330 (Reactome)
Active Trk

receptor complex: RIT/RIN-GTP:B- RAF

ComplexREACT_12347 (Reactome)
Active Trk receptor

complex:RIT/RIN- GTP

ComplexREACT_12211 (Reactome)
Active TrkA

receptor:ARMS:Crk complex

ComplexREACT_12251 (Reactome)
Active TrkA

receptor:Frs2 complex

ComplexREACT_12147 (Reactome)
Active TrkA

receptor:PLCG1 complex

ComplexREACT_12180 (Reactome)
Active TrkA

receptor:Phospho- ARMS:Crk complex

ComplexREACT_12282 (Reactome)
Active TrkA

receptor:Phospho- ARMS:Crk:C3G complex

ComplexREACT_12225 (Reactome)
Active TrkA

receptor:Phospho- Frs2 complex

ComplexREACT_12171 (Reactome)
Active TrkA

receptor:Phospho- Frs2:CrkL complex

ComplexREACT_12126 (Reactome)
Active TrkA

receptor:Phospho- Frs2:CrkL:C3G complex

ComplexREACT_12337 (Reactome)
Active TrkA

receptor:Phospho- PLCG1 complex

ComplexREACT_12153 (Reactome)
Active TrkA receptor

complex:RIT/RIN- GDP

ComplexREACT_12112 (Reactome)
Active TrkA:Phospho-

ARMS:Crk:C3G:Rap1- GTP complex

ComplexREACT_12359 (Reactome)
Active TrkA:Phospho-

ARMS:Crk:C3G:Rap1: Phospho-B-Raf complex

ComplexREACT_12169 (Reactome)
Active c-Src (p-

Y419)

ProteinP12931-1 (UniProt)
Adenosine A2a

receptor

ProteinP29274 (UniProt)
Adenosine:Adenosine

A2a receptor

ComplexREACT_11028 (Reactome)
Adenylate cyclase

(Mg2+ cofactor)

ComplexREACT_17689 (Reactome)
B-Raf (Zn2+

cofactor)

ComplexREACT_12124 (Reactome)
B-Raf complex ComplexREACT_12219 (Reactome)
B-Raf complex ComplexREACT_12300 (Reactome)
BAD protein ProteinQ92934 (UniProt)
C-terminal modulator

protein

ProteinQ5T1C6 (UniProt)
C3G ProteinREACT_12233 (Reactome)
C3G ProteinREACT_12261 (Reactome)
CDK inhibitor ProteinREACT_13380 (Reactome)
CREB ProteinP16220 (UniProt)
CaMKIV ProteinQ16566 (UniProt)
Calcium Metabolite29108 (ChEBI)
Calmodulin ProteinP62158 (UniProt)
Calmodulin:CaMK IV ComplexREACT_15739 (Reactome)
Calmodulin:CaMK IV ComplexREACT_15747 (Reactome)
Cam-PDE 1

homodimer

ComplexREACT_5507 (Reactome)
Caspase-9 ProteinP55211 (UniProt) any remaining instances associated here should be reassociated with the complex Cleaved Caspase-9
Clathrin-coated

vesicle

ComplexREACT_13103 (Reactome)
CrkL (SH3 domain) ProteinREACT_12190 (Reactome)
Cyclic-AMP-

dependent transcription factor ATF-1

ProteinP18846 (UniProt)
Dynamin-1/2/3 UnknownREACT_22651 (Reactome)
Dynein light chain ProteinO96015 (UniProt)
ELK1 ProteinREACT_13391 (Reactome)
ERK-specific DUSP UnknownREACT_12976 (Reactome)
ERK1/2/5 ProteinREACT_13316 (Reactome)
ERK5 ProteinQ13164 (UniProt)
Endophilin ProteinQ99962 (UniProt)
Forkhead box

transcription factor

ProteinREACT_13013 (Reactome)
Frs2 ProteinQ8WU20 (UniProt)
GDP Metabolite17552 (ChEBI)
GRB2:SOS1 ComplexREACT_4435 (Reactome)
GRB2:SOS:Phospho-

SHC

ComplexREACT_2380 (Reactome)
GRK2 ProteinP25098 (UniProt)
GRK2:calmodulin ComplexREACT_17570 (Reactome)
GSK3 ProteinREACT_13050 (Reactome)
GTP Metabolite15996 (ChEBI)
Guanine nucleotide

exchange factor

UnknownREACT_12202 (Reactome)
H2O Metabolite15377 (ChEBI)
IKKA ProteinO15111 (UniProt)
IP3 receptor

homotetramer

ComplexREACT_12247 (Reactome)
IP3 receptor:IP3

complex

ComplexREACT_12249 (Reactome)
IRS1/2 ProteinREACT_12744 (Reactome) The proteins mentioned here are examples of IRS family members acting as indicated for IRS. More family members are to be confirmed and added in the future.
Intracellular

Phosphorylated Trk receptor

ProteinREACT_10421 (Reactome)
Intracellular Trk

receptor

ProteinREACT_10478 (Reactome)
MAP kinase cascade PathwayREACT_634 (Reactome) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
MAP kinase p38

(Mg2+ cofactor)

ComplexREACT_12099 (Reactome)
MAPKAP kinase ProteinREACT_12293 (Reactome)
MDM2 ProteinQ00987 (UniProt)
MEF2 ProteinREACT_13049 (Reactome)
MEK5 ProteinQ13163 (UniProt)
MSK1 ProteinO75582 (UniProt)
NR4A1_Human ProteinP22736 (UniProt)
Orthophosphate Metabolite18367 (ChEBI)
PACAP:PACAP type 1

receptor

ComplexREACT_10139 (Reactome)
PDK1:AKT ComplexREACT_20806 (Reactome)
PDK1:AKT:PIP3 ComplexREACT_13226 (Reactome)
PHLPP (Mn2+

cofactor)

ComplexREACT_13329 (Reactome)
PI3K ComplexREACT_4240 (Reactome)
PIP3:PDK1:Phospho-

AKT

ComplexREACT_12841 (Reactome)
PIP3:PDK1:active AKT ComplexREACT_13230 (Reactome)
PIP3:RhoA ComplexREACT_12649 (Reactome)
PKA catalytic subunit ProteinREACT_3031 (Reactome)
PKA tetramer ComplexREACT_5749 (Reactome)
PKC-delta/epsilon ProteinREACT_12301 (Reactome)
PP2A-ABdeltaC

complex

ComplexREACT_2369 (Reactome)
PTEN (Mg2+

cofactor)

ComplexREACT_12877 (Reactome)
Phosphatidylinositol

-4,5-bisphosphate

Metabolite18348 (ChEBI)
Phosphatidylinositol-

3,4,5-trisphosphate

Metabolite16618 (ChEBI)
Phosphatidylinositol-

4,5-bisphosphate

Metabolite18348 (ChEBI)
Phospho-

ERK1/2/5

ProteinREACT_13301 (Reactome)
Phospho-

Phospholipase C gamma 1

ProteinP19174 (UniProt)
Phospho-AKT ProteinREACT_13006 (Reactome)
Phospho-BAD protein

(at S136)

ProteinQ92934 (UniProt)
Phospho-CDK

inhibitor

ProteinREACT_12999 (Reactome)
Phospho-Caspase-9 ProteinP55211 (UniProt) any remaining instances associated here should be reassociated with the complex Cleaved Caspase-9
Phospho-Cyclic-

AMP-dependent transcription factor ATF-1

ProteinP18846 (UniProt)
Phospho-ELK1 ProteinREACT_13225 (Reactome)
Phospho-ERK dimer UnknownREACT_12827 (Reactome)
Phospho-ERK5 ProteinQ13164 (UniProt)
Phospho-Forkhead

box transcription factor

ProteinREACT_13209 (Reactome)
Phospho-GSK3 ProteinREACT_13164 (Reactome)
Phospho-IKK1 (T23) ProteinO15111 (UniProt)
Phospho-IRS1/2:

PI3K(p85:p110)

ComplexREACT_12858 (Reactome)
Phospho-MAP kinase

p38 (Mg2+ cofactor)

ComplexREACT_12273 (Reactome)
Phospho-MAP kinase

p38 alpha/beta

ProteinREACT_12925 (Reactome)
Phospho-MAP kinase-

activated protein kinase 2

ProteinP49137 (UniProt)
Phospho-MDM2 ProteinQ00987 (UniProt)
Phospho-MEF2 ProteinREACT_12996 (Reactome)
Phospho-MSK1 ProteinO75582 (UniProt)
Phospho-Orphan

nuclear receptor NR4A1

ProteinP22736 (UniProt)
Phospho-PKC-

delta/epsilon

ProteinREACT_12203 (Reactome)
Phospho-Proline-rich

AKT1 substrate 1

ProteinQ96B36 (UniProt)
Phospho-Ribosomal

protein S6 kinase

ProteinREACT_12696 (Reactome)
Phospho-Ribosomal

protein S6 kinase 2

ProteinQ9UBS0 (UniProt)
Phospho-SHC ProteinREACT_12146 (Reactome)
Phospho-STAT3 ProteinREACT_12279 (Reactome)
Phospho-TSC2-1 ProteinP49815-1 (UniProt)
Phospholipase C

gamma 1

ProteinP19174 (UniProt)
Pituitary adenylate

cyclase activating polypeptide precursor

ProteinP18509 (UniProt)
Pituitary adenylate

cyclase activating polypeptide type I receptor

ProteinP41586 (UniProt)
Proline-rich AKT1

substrate 1

ProteinQ96B36 (UniProt)
Protein Kinase A,

catalytic subunits

ProteinREACT_2480 (Reactome)
RAF activation PathwayREACT_2077 (Reactome) Phosphorylated RAF is activated by Ras binding and stabilised in its active form by transient disassociation and reassociation of 14-3-3, as well as further phosphorylation.
RAL-GDP ComplexREACT_12274 (Reactome)
RAL-GTP ComplexREACT_12304 (Reactome)
RIT/RIN-GDP ComplexREACT_12139 (Reactome)
RalGDS ProteinQ12967 (UniProt)
Rap1-GDP ComplexREACT_12111 (Reactome)
Rap1-GDP ComplexREACT_12289 (Reactome)
Rap1-GTP ComplexREACT_12189 (Reactome)
Rap1-GTP ComplexREACT_12362 (Reactome)
Rap1-GTP:B-Raf

complex

ComplexREACT_12223 (Reactome)
Ras-GTP:RalGDS

complex

ComplexREACT_12340 (Reactome)
RhoA ProteinP61586 (UniProt)
Ribosomal protein S6

kinase

ProteinREACT_13229 (Reactome)
Ribosomal protein S6

kinase 2

ProteinQ9UBS0 (UniProt)
SRC ProteinP12931-1 (UniProt)
STAT3 ProteinREACT_12309 (Reactome)
Shc transforming

protein

ProteinREACT_12338 (Reactome)
TORC2 complex ComplexREACT_13222 (Reactome)
TSC2-1 ProteinP49815-1 (UniProt)
Tribbles homolog 3 ProteinQ96RU7 (UniProt)
TrkA-1

receptor

ProteinP04629-1 (UniProt)
active Cam-PDE 1 ComplexREACT_3728 (Reactome)
adenosine Metabolite16335 (ChEBI)
beta-NGF dimer:

TrkA receptor

ComplexREACT_10893 (Reactome)
beta-NGF dimer:

TrkA receptor dimer

ComplexREACT_10135 (Reactome)
cAMP:PKA regulatory

subunit

ComplexREACT_4571 (Reactome)
diacylglycerols Metabolite18035 (ChEBI)
mature beta-NGF

homodimer

ComplexREACT_10239 (Reactome)
p21 RAS:GDP ComplexREACT_2657 (Reactome)
p21 RAS:GTP ComplexREACT_4782 (Reactome)
phospho-CREB ProteinP16220 (UniProt)
phospho-CREB dimer ComplexREACT_17630 (Reactome)
phospho-CaMK IV:

Calmodulin

ComplexREACT_15743 (Reactome)
pyrophosphate Metabolite29888 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1873"
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