NGF activates the phosphorylation of MAP1B by GSK3beta through the TrkA receptor and not the p75(NTR) receptor
| Autor: | Robert G, Goold, Phillip R, Gordon-Weeks |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Neurons
Glycogen Synthase Kinase 3 beta Dose-Response Relationship Drug Carbazoles Chick Embryo Receptors Nerve Growth Factor PC12 Cells Receptor Nerve Growth Factor Axons Indole Alkaloids Rats Glycogen Synthase Kinase 3 Nerve Growth Factor Neurites Animals Phosphorylation Rats Wistar Receptor trkA Microtubule-Associated Proteins Cells Cultured |
| Zdroj: | Journal of neurochemistry. 87(4) |
| ISSN: | 0022-3042 |
| Popis: | We have recently shown that nerve growth factor (NGF) induces the phosphorylation of the microtubule-associated protein 1B (MAP1B) by activating the serine/threonine kinase glycogen synthase kinase 3beta (GSK3beta) in a spatio-temporal pattern in PC12 cells that correlates tightly with neurite growth. PC12 cells express two types of membrane receptor for NGF: TrkA receptors and p75NTR receptors, and it was not clear from our studies which receptor was responsible. We show here that brain-derived neurotrophic factor, which activates p75NTR but not TrkA receptors, does not stimulate GSK3beta phosphorylation of MAP1B in PC12 cells. Similarly, NGF fails to activate GSK3beta phosphorylation of MAP1B in PC12 cells that lack TrkA receptors but express p75NTR receptors (PC12 nnr). Chick ciliary ganglion neurons in culture lack TrkA receptors but express p75NTR and also fail to show NGF-dependent GSK3beta phosphorylation of MAP1B, whereas in rat superior cervical ganglion neurons in culture, NGF activation of TrkA receptors elicits GSK3beta phosphorylation of MAP1B. Finally, inhibition of TrkA receptor tyrosine kinase activity in PC12 cells and superior cervical ganglion neurons with K252a potently and dose-dependently inhibits neurite elongation while concomitantly blocking GSK3beta phosphorylation of MAP1B. These results suggest that the activation of GSK3beta by NGF is mediated through the TrkA tyrosine kinase receptor and not through p75NTR receptors. |
| Databáze: | OpenAIRE |
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