KEGG PATHWAY: hsa04722

PATHWAY: hsa04722

Entry

hsa04722 Pathway

Name

Neurotrophin signaling pathway - Homo sapiens (human)

Description

Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory.

Class

Organismal Systems; Nervous system

Pathway map

hsa04722

Neurotrophin signaling pathway

Disease

H00078	Frontotemporal lobar degeneration (FTLD)
H00408	Type I diabetes mellitus
H00681	Acne inversa
H00916	Congenital central hypoventilation syndrome (CCHS)
H01007	Choroid plexus papilloma
H01018	Metachondromatosis

Drug

D08869	Begacestat (USAN/INN)
D09010	Tarenflurbil (USAN/INN)
D09377	Semagacestat (USAN/INN)
D09387	Tanezumab (USAN/INN)
D09869	Avagacestat (USAN)
D09907	Fulranumab (USAN/INN)
D10334	Rebastinib (USAN)

Organism

Homo sapiens (human) [GN:hsa]

Gene

4803	NGF; nerve growth factor (beta polypeptide) [KO:K02582]
627	BDNF; brain-derived neurotrophic factor [KO:K04355]
4909	NTF4; neurotrophin 4 [KO:K12457]
4908	NTF3; neurotrophin 3 [KO:K04356]
4914	NTRK1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
4915	NTRK2; neurotrophic tyrosine kinase, receptor, type 2 [KO:K04360] [EC:2.7.10.1]
4916	NTRK3; neurotrophic tyrosine kinase, receptor, type 3 [KO:K05101] [EC:2.7.10.1]
10603	SH2B2; SH2B adaptor protein 2 [KO:K07193]
25970	SH2B1; SH2B adaptor protein 1 [KO:K12459]
10019	SH2B3; SH2B adaptor protein 3 [KO:K12459]
2885	GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654	SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
673	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
5604	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197	RPS6KA3; ribosomal protein S6 kinase, 90kDa, polypeptide 3 [KO:K04373] [EC:2.7.11.1]
6195	RPS6KA1; ribosomal protein S6 kinase, 90kDa, polypeptide 1 [KO:K04373] [EC:2.7.11.1]
6196	RPS6KA2; ribosomal protein S6 kinase, 90kDa, polypeptide 2 [KO:K04373] [EC:2.7.11.1]
27330	RPS6KA6; ribosomal protein S6 kinase, 90kDa, polypeptide 6 [KO:K04373] [EC:2.7.11.1]
9252	RPS6KA5; ribosomal protein S6 kinase, 90kDa, polypeptide 5 [KO:K04445] [EC:2.7.11.1]
468	ATF4; activating transcription factor 4 (tax-responsive enhancer element B67) [KO:K04374]
596	BCL2; B-cell CLL/lymphoma 2 [KO:K02161]
57498	KIDINS220; kinase D-interacting substrate, 220kDa [KO:K12460]
10818	FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
1398	CRK; v-crk sarcoma virus CT10 oncogene homolog (avian) [KO:K04438]
1399	CRKL; v-crk sarcoma virus CT10 oncogene homolog (avian)-like [KO:K04438]
2889	RAPGEF1; Rap guanine nucleotide exchange factor (GEF) 1 [KO:K06277]
5906	RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908	RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
4215	MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
5607	MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
5598	MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
5600	MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300	MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603	MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432	MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
9261	MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
25759	SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K06279]
399694	SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K06279]
53358	SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K06279]
6464	SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
2549	GAB1; GRB2-associated binding protein 1 [KO:K09593]
5295	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5290	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293	PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
207	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
4793	NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
4792	NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4794	NFKBIE; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon [KO:K05872]
4790	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
2309	FOXO3; forkhead box O3 [KO:K09408]
356	FASLG; Fas ligand (TNF superfamily, member 6) [KO:K04389]
572	BAD; BCL2-associated agonist of cell death [KO:K02158]
2932	GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
5163	PDK1; pyruvate dehydrogenase kinase, isozyme 1 [KO:K12077] [EC:2.7.11.2]
3667	IRS1; insulin receptor substrate 1 [KO:K16172]
5335	PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
5336	PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
810	CALML3; calmodulin-like 3 [KO:K02183]
805	CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808	CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801	CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688	CALML6; calmodulin-like 6 [KO:K02183]
51806	CALML5; calmodulin-like 5 [KO:K02183]
815	CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817	CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816	CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818	CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
814	CAMK4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
25	ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
5781	PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
4145	MATK; megakaryocyte-associated tyrosine kinase [KO:K08888] [EC:2.7.10.2]
4804	NGFR; nerve growth factor receptor [KO:K02583]
397	ARHGDIB; Rho GDP dissociation inhibitor (GDI) beta [KO:K12462]
396	ARHGDIA; Rho GDP dissociation inhibitor (GDI) alpha [KO:K12462]
398	ARHGDIG; Rho GDP dissociation inhibitor (GDI) gamma [KO:K12462]
387	RHOA; ras homolog family member A [KO:K04513]
998	CDC42; cell division cycle 42 [KO:K04393]
5879	RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
4214	MAP3K1; mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase [KO:K04416] [EC:2.7.11.25]
4217	MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
5609	MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
5599	MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602	MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601	MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725	JUN; jun proto-oncogene [KO:K04448]
7157	TP53; tumor protein p53 [KO:K04451]
581	BAX; BCL2-associated X protein [KO:K02159]
7161	TP73; tumor protein p73 [KO:K10148]
7189	TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
10782	ZNF274; zinc finger protein 274 [KO:K12458]
11108	PRDM4; PR domain containing 4 [KO:K12463]
9500	MAGED1; melanoma antigen family D, 1 [KO:K12464]
27018	NGFRAP1; nerve growth factor receptor (TNFRSF16) associated protein 1 [KO:K12465]
7531	YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
8767	RIPK2; receptor-interacting serine-threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
3654	IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
3656	IRAK2; interleukin-1 receptor-associated kinase 2 [KO:K04731] [EC:2.7.11.1]
11213	IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
51135	IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3551	IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
6272	SORT1; sortilin 1 [KO:K12388]
5663	PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5664	PSEN2; presenilin 2 (Alzheimer disease 4) [KO:K04522] [EC:3.4.23.-]
5580	PRKCD; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]

Compound

C00076	Calcium cation
C00165	Diacylglycerol
C00195	N-Acylsphingosine
C01245	D-myo-Inositol 1,4,5-trisphosphate
C05981	Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:12676795

Authors

Huang EJ, Reichardt LF.

Title

Trk receptors: roles in neuronal signal transduction.

Journal

Annu Rev Biochem 72:609-42 (2003)

Reference

PMID:11399424

Authors

Patapoutian A, Reichardt LF

Title

Trk receptors: mediators of neurotrophin action.

Journal

Curr Opin Neurobiol 11:272-80 (2001)

Reference

PMID:16699811

Authors

Arevalo JC, Wu SH

Title

Neurotrophin signaling: many exciting surprises!

Journal

Cell Mol Life Sci 63:1523-37 (2006)

Reference

PMID:14704852

Authors

Teng KK, Hempstead BL

Title

Neurotrophins and their receptors: signaling trios in complex biological systems.

Journal

Cell Mol Life Sci 61:35-48 (2004)

Reference

PMID:11529497

Authors

Miller FD, Kaplan DR

Title

Neurotrophin signalling pathways regulating neuronal apoptosis.

Journal

Cell Mol Life Sci 58:1045-53 (2001)

Reference

PMID:10851172

Authors

Kaplan DR, Miller FD

Title

Neurotrophin signal transduction in the nervous system.

Journal

Curr Opin Neurobiol 10:381-91 (2000)

Reference

PMID:16939974

Authors

Reichardt LF

Title

Neurotrophin-regulated signalling pathways.

Journal

Philos Trans R Soc Lond B Biol Sci 361:1545-64 (2006)

Reference

PMID:16856873

Authors

Zampieri N, Chao MV

Title

Mechanisms of neurotrophin receptor signalling.

Journal

Biochem Soc Trans 34:607-11 (2006)

Reference

PMID:15499580

Authors

Rose CR, Blum R, Kafitz KW, Kovalchuk Y, Konnerth A

Title

From modulator to mediator: rapid effects of BDNF on ion channels.

Journal

Bioessays 26:1185-94 (2004)

Reference

PMID:10812966

Authors

Yano H, Chao MV

Title

Neurotrophin receptor structure and interactions.

Journal

Pharm Acta Helv 74:253-60 (2000)

Reference

PMID:10764727

Authors

Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA

Title

NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.

Journal

J Biol Chem 275:17566-70 (2000)

Reference

PMID:10985348

Authors

Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA

Title

NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis.

Journal

Neuron 27:279-88 (2000)

KO pathway

ko04722

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Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (6)   
   KEGG DISEASE (6)   
Drug (7)   
   KEGG DRUG (7)   
Genome (1)   
   KEGG GENOME (1)   
Gene (120)   
   KEGG GENES (120)   
All databases (137)   

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