NGF Signaling / Pathway

An Overview of NGF Signaling / Pathway

Binding interaction between NGF and the TrkA receptor facilitates receptor dimerization and tyrosine residue phosphorylation of the cytoplasmic tail by adjacent Trk receptors. Trk receptor phosphorylation sites operate as Shc adaptor protein docking sites, which undergo phosphorylation by the TrkA receptor. Once the cytoplasmic adaptor protein (Shc) is phosphorylated by the receptor cytoplasmic tail, cell survival is initiated through several intracellular pathways (figure 1).

NGF Signaling / Pathway to Active Akt

One major pathway leads to the activation of the serine/threonine kinase, Akt. This pathway begins with the Trk receptor complex-recruitment of a second adaptor protein called growth factor-receptor bound protein-2 (Grb2) along with a docking protein called Grb2-associated Binder-1 (GAB1). Subsequently, phosphatidylinositol-3 kinase (PI3K) is activated, resulting in Akt kinase activation. Study results have shown that blocking PI3K or Akt activity results in death of sympathetic neurons in culture, regardless of NGF presence. However if either kinase is constitutionally active, neurons survive even without NGF.

NGF Signaling / Pathway to Cell Survival

A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase. In this pathway, recruitment of a guanine nucleotide exchange factor by the adaptor and docking proteins leads to activation of a membrane-associated G-protein known as Ras. The guanine nucleotide exchange factor mediates Ras activation through the GDP-GTP exchange process. The active Ras protein phosphorylates several proteins, along with the serine/ threonine kinase, Raf. Raf, in turn activates the MAPK cascade to facilitate ribosomal s6 kinase (RSK) activation and transcriptional regulation.

Summary of NGF Signaling / Pathway

Both Akt and RSK, components of the PI3K-Akt and MAPK pathways respectively, act to phosphorylate the cyclic AMP response element binding protein (CREB) transcription factor. Phosphorylated CREB translocates into the nucleus and mediates increased expression of anti-apoptotic proteins, thus promoting NGF-mediated cell survival. However, in the absence of NGF, the expression of pro-apoptotic proteins is increased when the activation of cell death-promoting transcription factors such as c-Jun are not suppressed by the aforementioned NGF-mediated cell survival pathways.

NGF signaling

Figure 1: NGF signaling / pathway

23000+ Products
Proteins
Antibodies
ELISA Kits
cDNA Clones
Recombinant Cytokines
Neurotrophin & Receptor
NGF Related Information +
- NGF molecular weight
- NGF structure
- NGF function
- NGF signaling / pathway
- NGF receptor
-- NGF TrkA
-- NGFR / p75
BDNF Related Information +
- BDNF Gene
- BDNF function
- BDNF signaling / pathway
- BDNF receptor
-- BDNF TrkB
-- NGFR / p75
• Other Neurotrophin & Receptor+
- Neurotrophin-3 / NT-3
- TrkA / NTRK1
- TrkB / NTRK2
- TrkC / NTRK3
- NGFR (p75 / p75 NTR)
GDNF Family
GDNF (Glial cell line-derived neurotrophin)
GFRA1
GFRA2
GFRA3
NCAM / CD56
Other Neurotrophic Factors & Receptors
MANF / ARMET
Gp130 / IL6ST
LIFR / CD118
CNTF / Ciliary Neurotrophic Factor
CDNF / ARMETL1
NRG1 / Neuregulin 1
NRG4 / Neuregulin 4
Pleiotrophin / PTN
CNTFR
Growth Factor Family
Angiopoietin/Tie
Ephrin & Eph Receptor
EGF & Receptor
FGF & Receptor
Insulin-like Growth Factor System
Neurotrophin & Receptor
PDGF & Receptor
Receptor Tyrosine Kinase
R-Spondin Protein
VEGF & Receptor
Wnt Ligands & Receptors