THE PHOSPHOPROTEIN STATHMIN IS ESSENTIAL FOR NERVE GROWTH FACTOR-STIMULATED DIFFERENTIATION

Stathmin is a ubiquitous cytosolic protein which undergoes extensive p hosphorylation in response to a variety of external signals. It is hig hly abundant in developing neurons. The use of antisense oligonucleoti des which selectively block stathmin expression has allowed us to stud y 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 severa l NGF-inducible genes was not affected. Furthermore, we found that sta thmin phosphorylation in PC12 cells which is induced by NGF depends on mitogen-activated protein kinase (MAPK) activity, We conclude that st athmin is an essential component of the NGF-induced MAPK signaling pat hway and performs a key role during differentiation of developing neur ons.