Brain-derived neurotrophic factor stimulates phosphorylation of stathmin in cortical neurons.
We have identified by two-dimensional polyacrylamide gel electrophoresis a protein known as stathmin which is phosphorylated in a time- and concentration-dependent manner in response to brain-derived neurotrophic factor (BDNF) in primary cultures of cortical neurons. We show that stathmin phosphorylation is preceded by the activation of mitogen-activated protein kinase (MAPK) isoforms p44 and p42. Moreover, the MAPK kinase inhibitor PD 098059, which inhibits MAPK activation, also markedly reduces BDNF-stimulated phosphorylation of stathmin, therefore suggesting that phosphorylation of stathmin is triggered by the activation of MAPK. Phosphorylation of stathmin is specific for BDNF since nerve growth factor does not stimulate MAPK and stathmin phosphorylation in cultured cortical neurons. Taken together, these results identify stathmin as a new target protein of BDNF, possibly involved in the development of cortical neurons.
Cardinaux
J R
JR
Institut de Physiologie et Service de Neurologie du CHUV, Faculté de Médecine, Université de Lausanne, Switzerland.
Magistretti
P J
PJ
Martin
J L
JL
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008868:Microtubule Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D050777:Stathmin
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008868:Microtubule Proteins; D010710:Phosphates; D010750:Phosphoproteins; D050777:Stathmin; C493994:Stmn1 protein, mouse; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one