Phosphorylation of the growth factors bFGF, NGF and BDNF: a prerequisite for their biological activity
| Autor: | Susanne Klumpp, Dorothee Kriha, Stefanie Pallast, Josef Krieglstein, Patrick Hoell, Gunther Bechmann, Sandra Maier, Alexander Maaßen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Basic fibroblast growth factor Biology Hippocampus Dephosphorylation Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Adenosine Triphosphate Internal medicine Nerve Growth Factor medicine Animals Phosphorylation Cells Cultured Brain-derived neurotrophic factor Cerebral Cortex Growth factor Brain-Derived Neurotrophic Factor Autophosphorylation Cell Biology Rats Nerve growth factor Endocrinology chemistry Alkaline phosphatase Fibroblast Growth Factor 2 |
| Zdroj: | Neurochemistry international. 48(2) |
| ISSN: | 0197-0186 |
| Popis: | The aim of this work was to test whether growth factors such as basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) undergo autophosphorylation and whether this affects their biological activity. Incubation of those growth factors with [γ- 32 P]ATP resulted in phosphorylation in vitro. The phosphate bond was resistant to alkaline pH, yet acid-labile. Addition of alkaline phosphatase resulted in time and protein dependent dephosphorylation. Concomitantly, alkaline phosphatase abolished the neuroprotective effect of those growth factors upon oxygen and glucose deprivation and upon staurosporine-induced cell death. For those studies, we were using primary cultures of cortical and hippocampal neurons from embryonic and neonatal rats. Incubation of bFGF with non-hydrolyzable ATP-γS resulted in phosphorylation and in neuroprotection resistant to alkaline phosphatase. We conclude that bFGF, NGF and BDNF undergo autophosphorylation on site(s) other than serine, threonine, tyrosine and/or ATP-binding, and that this binding of phosphate is essential for neuroprotection in vivo. |
| Databáze: | OpenAIRE |
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