The phosphoprotein stathmin is essential for nerve growth factor-stimulated differentiation.
Stathmin is a ubiquitous cytosolic protein which undergoes extensive phosphorylation in response to a variety of external signals. It is highly abundant in developing neurons. The use of antisense oligonucleotides which selectively block stathmin expression has allowed us to study directly its role in rat PC12 cells. We show that stathmin depletion prevents nerve growth factor (NGF)-stimulated differentiation of PC12 cells into sympathetic-like neurons although the expression of several NGF-inducible genes was not affected. Furthermore, we found that stathmin phosphorylation in PC12 cells which is induced by NGF depends on mitogen-activated protein kinase (MAPK) activity. We conclude that stathmin is an essential component of the NGF-induced MAPK signaling pathway and performs a key role during differentiation of developing neurons.
Di Paolo
G
G
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Pellier
V
V
Catsicas
M
M
Antonsson
B
B
Catsicas
S
S
Grenningloh
G
G
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016501:Neurites; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D064531:Peripherins; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D050777:Stathmin; D013873:Thionucleotides / Q000494:pharmacology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D005419:Flavonoids; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense; D064531:Peripherins; D010750:Phosphoproteins; D050777:Stathmin; C512848:Stmn2 protein, rat; D013873:Thionucleotides; C062040:Vgf protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one