THE MICROTUBULE-DESTABILIZING ACTIVITY OF METABLASTIN (P19) IS CONTROLLED BY PHOSPHORYLATION

Metablastin (also called p19, stathmin, prosolin, p18, Lap18, and onco protein 18) is a highly conserved, cytosolic 149-amino acid polypeptid e that is expressed in immature vertebrate cells and undergoes extrace llular factor- and cell cycle-regulated serine phosphorylation. The pr otein was shown recently to destabilize microtubules in vitro (Belmont , L., and Mitchison, T. J. (1996) Cell 84, 623-631). Here we demonstra te that microinjection of recombinant metablastin induces a loss of mi crotubules in COS-7 cells. This effect is enhanced by serine-to-alanin e mutations at several phosphorylation sites and virtually abolished b y aspartate substitution at a single site, Ser-63. We also show that s toichiometric amounts of metablastin prevent assembly and promote disa ssembly of microtubules in vitro. Interestingly, the phosphorylation s ite mutations of metablastin that have dramatic differential effects i n intact cells do not alter the ability of metablastin to block tubuli n assembly in vitro. The data suggest that phosphorylation of metablas tin controls its microtubule-destabilizing activity in vivo but that t his regulation may require additional cellular factors. This control m echanism is poised to play a critical role in the dynamic reorganizati on of the cellular microtubule network that occurs during morphogenesi s and mitosis.