NGF Signaling
A fundamental issue in current biology is the question of maintaining a critical balance between cell survival and cell death, both during development and in adulthood. In the nervous system, a family of neurotrophins which includes nerve growth factor (NGF), BDNF, and neurotrophins 3/4/5, maintains this critical balance. The best characterized of these is NGF, a neurotrophic protein which is important for the growth and survival of diverse peripheral and central neurons. It is expressed within discrete CNS areas and is secreted by tissues targeted by sympathetic and some sensory neurons. The effects of NGF on neuronal growth and survival are mediated by a high affinity cell surface receptor TrkA and a low affinity receptor p75(NTR)...
Pathway Summary
A fundamental issue in current biology is the question of maintaining a critical balance between cell survival and cell death, both during development and in adulthood. In the nervous system, a family of neurotrophins which includes nerve growth factor (NGF), BDNF, and neurotrophins 3/4/5, maintains this critical balance. The best characterized of these is NGF, a neurotrophic protein which is important for the growth and survival of diverse peripheral and central neurons. It is expressed within discrete CNS areas and is secreted by tissues targeted by sympathetic and some sensory neurons. The effects of NGF on neuronal growth and survival are mediated by a high affinity cell surface receptor TrkA and a low affinity receptor p75(NTR).Activation of TrkA by NGF is followed by receptor dimerization and trans-autophosphorylation of tyrosine residues on TrkA, which then act as docking sites for a variety of downstream signaling effectors and adaptor proteins. Adaptor proteins such as SOS and GRB2 are recruited to TrkA leading to activation of the Ras-Raf-MEK-ERK, PI3K-AKT signaling pathways. PLC-γ phosphorylation results in the activation of the PKC signaling pathway. The Rac-RhoA-ROCK pathway results in actin polymerization and neurite outgrowth and differentiation, while AKT signaling regulates neuronal survival.NGF binds with lower affinity to p75(NTR), which has no tyrosine kinase domain. The main physiological function of p75(NTR) is to activate TrkA-independent signal transduction cascades involving sphingomyelinase, NF-κB and JNK. p75(NTR) activates a survival pathway that may involve the activation of NF-κB through TRAF-6, whereas limiting amounts of p75(NTR) may activate the JNK death signaling pathway. p75(NTR) can also activate sphingomyelinase to produce ceramide. Ceramide is a key player in the induction of neuronal apoptosis.NGF is the most potent growth factor for cholinergic neurons and it influences the proliferation, differentiation, survival and death of neurons. It is essential for the health and well-being of the nervous system. Alterations in NGF levels have been implicated in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease, as well as psychiatric disorders such as depression and substance abuse. It is a promising candidate for treating Alzheimer's disease.
NGF Signaling Genes list
Explore Genes related to NGF Signaling
AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 ATF2activating transcription factor 2 ATF4activating transcription factor 4 BAXBCL2 associated X, apoptosis regulator CDC42cell division cycle 42 CHUKcomponent of inhibitor of nuclear factor kappa B kinase complex CREB1cAMP responsive element binding protein 1 CREB3cAMP responsive element binding protein 3 CREB3L1cAMP responsive element binding protein 3 like 1 CREB3L2cAMP responsive element binding protein 3 like 2 CREB3L3cAMP responsive element binding protein 3 like 3 CREB3L4cAMP responsive element binding protein 3 like 4 CREB5cAMP responsive element binding protein 5 CREBBPCREB binding protein CRKCRK proto-oncogene, adaptor protein ELK1ETS transcription factor ELK1 ERASES cell expressed Ras GAB1GRB2 associated binding protein 1 GRB2growth factor receptor bound protein 2 HRASHRas proto-oncogene, GTPase IKBKBinhibitor of nuclear factor kappa B kinase subunit beta IKBKEinhibitor of nuclear factor kappa B kinase subunit epsilon IKBKGinhibitor of nuclear factor kappa B kinase regulatory subunit gamma KRASKRAS proto-oncogene, GTPase MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP2K4mitogen-activated protein kinase kinase 4 MAP3K1mitogen-activated protein kinase kinase kinase 1 MAP3K10mitogen-activated protein kinase kinase kinase 10 MAP3K11mitogen-activated protein kinase kinase kinase 11 MAP3K12mitogen-activated protein kinase kinase kinase 12 MAP3K13mitogen-activated protein kinase kinase kinase 13 MAP3K14mitogen-activated protein kinase kinase kinase 14 MAP3K15mitogen-activated protein kinase kinase kinase 15 MAP3K2mitogen-activated protein kinase kinase kinase 2 MAP3K3mitogen-activated protein kinase kinase kinase 3 MAP3K4mitogen-activated protein kinase kinase kinase 4 MAP3K5mitogen-activated protein kinase kinase kinase 5 MAP3K6mitogen-activated protein kinase kinase kinase 6 MAP3K7mitogen-activated protein kinase kinase kinase 7 MAP3K8mitogen-activated protein kinase kinase kinase 8 MAP3K9mitogen-activated protein kinase kinase kinase 9 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK12mitogen-activated protein kinase 12 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MAPK7mitogen-activated protein kinase 7 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MRASmuscle RAS oncogene homolog NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NGFnerve growth factor NGFRnerve growth factor receptor NRASNRAS proto-oncogene, GTPase NTRK1neurotrophic receptor tyrosine kinase 1 PDPK13-phosphoinositide dependent protein kinase 1 PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PLCG1phospholipase C gamma 1 PLCG2phospholipase C gamma 2 PRKCDprotein kinase C delta PRKCZprotein kinase C zeta PTPN11protein tyrosine phosphatase non-receptor type 11 RAC1Rac family small GTPase 1 RAF1Raf-1 proto-oncogene, serine/threonine kinase RALARAS like proto-oncogene A RALBRAS like proto-oncogene B RAP1ARAP1A, member of RAS oncogene family RAP1BRAP1B, member of RAS oncogene family RAP2ARAP2A, member of RAS oncogene family RAP2BRAP2B, member of RAS oncogene family RASD1ras related dexamethasone induced 1 RASD2RASD family member 2 RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit RHOAras homolog family member A RHOGras homolog family member G ROCK1Rho associated coiled-coil containing protein kinase 1 ROCK2Rho associated coiled-coil containing protein kinase 2 RPS6KA1ribosomal protein S6 kinase A1 RPS6KA2ribosomal protein S6 kinase A2 RPS6KA3ribosomal protein S6 kinase A3 RPS6KA4ribosomal protein S6 kinase A4 RPS6KA5ribosomal protein S6 kinase A5 RPS6KA6ribosomal protein S6 kinase A6 RPS6KB1ribosomal protein S6 kinase B1 RPS6KB2ribosomal protein S6 kinase B2 RPS6KC1ribosomal protein S6 kinase C1 RRASRAS related RRAS2RAS related 2 SHC1SHC adaptor protein 1 SHC2SHC adaptor protein 2 SHC3SHC adaptor protein 3 SMPD1sphingomyelin phosphodiesterase 1 SMPD2sphingomyelin phosphodiesterase 2 SMPD3sphingomyelin phosphodiesterase 3 SMPD4sphingomyelin phosphodiesterase 4 SOS1SOS Ras/Rac guanine nucleotide exchange factor 1 SOS2SOS Ras/Rho guanine nucleotide exchange factor 2 TP53tumor protein p53 TRAF4TNF receptor associated factor 4 TRAF6TNF receptor associated factor 6 TRIOtrio Rho guanine nucleotide exchange factor
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