Neurotrophin signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
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Neurotrophin signaling pathway - Homo sapiens (human) cluster_node43 Outside Neuron cluster_Membrane Membrane cluster_node44 gamma-secretase cluster_node45 !braf cluster_node46 !actin cluster_node47 !mapk cluster_node48 !plas p75ICD node1 3 node2 1 node3 2 node2->node3 +p growth factor receptor-bound protein 2 GRB2 node2->GRB2 cAbl node2->cAbl Shc node2->Shc +p IRS node2->IRS +p CHK node2->CHK PLCgamma node2->PLCgamma ARMS v-crk sarcoma virus CT10 oncogene homolog (avian) CRK ARMS->CRK fibroblast growth factor receptor substrate 2 FRS2 FRS2->CRK rAPS rAPS->GRB2 SH2B SH2B->GRB2 node3->rAPS node3->SH2B C3G CRK->C3G Rapl C3G->Rapl node4 B-Raf Rapl->node4 MEKK3 MEK5 MEKK3->MEK5 +p Erk5 MEK5->Erk5 +p p90RSK Erk5->p90RSK +p node5 2 p38 p38->node5 p38 mitogen-activated protein kinase-activated protein kinase 2 MAPKAPK2 p38->MAPKAPK2 +p CREB MAPKAPK2->CREB p90RSK->CREB +p Ras p90RSK->Ras +p MSK1 MSK1->p90RSK node6 1 CREB->node6 CREB DNA 1 CREB->DNA 1 node8 Bcl-2 DNA 1->node8 node7 21 SOS GRB2->SOS node18 SH-PTP2 GRB2->node18 node9 2 SOS->node9 SOS SOS->Ras node10 1 Ras->MEKK3 Ras->p38 +p Ras->node10 Ras Raf Ras->Raf PI3K Ras->PI3K node11 4 Raf->node11 Raf node13 MEK1/2 Raf->node13 +p node12 2 node13->node12 MEK1/2 node15 Erk1/2 node13->node15 +p node14 15 node15->p90RSK +p node15->Ras +p node15->node14 Erk1/2 Shc->GRB2 GRB2-associated binding protein 1 GAB1 Shc->GAB1 node16 4 IRS->node16 IRS IRS->PI3K DAG PLCgamma->DAG IP3 PLCgamma->IP3 GAB1->PI3K node17 12 PI3K->node17 PI3K PIP3 PI3K->PIP3 node18->PI3K node19 3 PIP3->node19 PIP3 PDK PIP3->PDK AKT PIP3->AKT PDK->AKT node20 29 AKT->node20 AKT IkB AKT->IkB +p FKHRL1 AKT->FKHRL1 +p BCL2-associated agonist of cell death BAD AKT->BAD +p glycogen synthase kinase 3 beta GSK3B AKT->GSK3B +p PKCdelta PKCdelta->node13 Regulation of actin cytoskeleton PKCdelta->Regulation of actin cytoskeleton DAG->PKCdelta node21 CA2+ IP3->node21 CaM node21->CaM CaMK CaM->CaMK CREB 2 CaMK->CREB 2 CaMK->Regulation of actin cytoskeleton ceramide ceramide->PI3K Ubiquitin mediated proteolysis node22 4 IkB->Ubiquitin mediated proteolysis IkB->node22 IkB NFkB IkB->NFkB node23 32 NFkB->node23 NFkB DNA 2 NFkB->DNA 2 Cell Survival 2 DNA 2->Cell Survival 2 Retrograde transport 2 DNA 2->Retrograde transport 2 node24 1 FKHRL1->node24 FKHRL1 DNA 3 FKHRL1->DNA 3 FasL DNA 3->FasL FasL->Cell Survival 2 node25 2 BAD->Cell Survival 2 BAD->node25 BAD node26 5 GSK3B->Cell Survival 2 GSK3B->node26 GSK3B GSK3B->Regulation of actin cytoskeleton Plasticity CREB 2->Plasticity RhoGDI ras homolog gene family,member A RHOA RhoGDI->RHOA RHOA->Regulation of actin cytoskeleton node27 SC-1 Cell cycle arrest node27->Cell cycle arrest NRAGE Apoptosis NRAGE->Apoptosis NRAGE->Cell cycle arrest node28 3 TNF receptor-associated factor 6 TRAF6 TRAF6->node28 TRAF6 NRIF TRAF6->NRIF +u JNK TRAF6->JNK cell division cycle 42 (GTP binding protein,25kDa) CDC42 node29 CDC42 RAC1 node30 MAP3K1 MAP3K5 node29->node30 MKK7 node30->MKK7 MKK7->JNK node31 11 JNK->node31 JNK p53 JNK->p53 node35 c-Jun JNK->node35 p73 p73->p53 node32 10 p53->node32 p53 BCL2-associated X protein BAX p53->BAX node33 16 BAX->node33 BAX BAX->Apoptosis DNA 4 DNA 4->Apoptosis node34 1 node35->DNA 4 node35->node34 c-Jun NADE node36 14-3 -3epsilon NADE->node36 node36->Apoptosis RIP2 node37 2 IRAK IRAK->node37 IRAK IKKbeta IRAK->IKKbeta node38 3 TRAF6 2 TRAF6 2->node38 TRAF6 2 TRAF6 2->IKKbeta node39 2 IKKbeta->node39 IKKbeta IkB 2 IKKbeta->IkB 2 +p node40 4 IkB 2->node40 IkB 2 NFkB 2 IkB 2->NFkB 2 node41 29 NFkB 2->node41 NFkB 2 DNA 5 NFkB 2->DNA 5 Cell Survival 3 DNA 5->Cell Survival 3 node4->node13 brain-derived neurotrophic factor BDNF TrkB BDNF->TrkB p75NTR BDNF->p75NTR TrkB->node2 p75NTR->ceramide p75NTR->RhoGDI p75NTR->RHOA p75NTR->node27 p75NTR->NRAGE p75NTR->TRAF6 p75NTR->NRIF p75NTR->node29 p75NTR->NADE p75NTR->RIP2 p75NTR->IRAK p75NTR->TRAF6 2 p75CTF p75NTR->p75CTF extracellular domain p75NTR->extracellular domain node8->node7 Bcl-2 nerve growth factor (beta polypeptide) NGF NGF->p75NTR TrkA NGF->TrkA TrkA->node2 TrkA->ARMS +p TrkA->FRS2 3'-nucleotidase NT3 NT3->TrkB NT3->p75NTR NT3->TrkA TrkC NT3->TrkC TrkC->node2 NT4 NT4->TrkB NT4->p75NTR PSEN PSEN->node1 PSEN PSEN->p75CTF p75CTF->p75ICD p75BetaP p75CTF->p75BetaP Sortilin Sortilin->p75NTR MAPK Signaling Pathway Axonal outgrowth Retrograde transport Cellular differentiation Membrane ruffling Axonal guidance Cell Survival 1 Axon patterning node42 Long-term potentiation (LTP) Axonal growth Synapse formation print "