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J. Cell Biol.,
Volume 140, Number 1, January 12, 1998 131-141
The Department for Cell and Molecular Biology, University of Umeå, S-901 87 Sweden
Oncoprotein 18 (Op18, also termed p19,
19K, metablastin, stathmin, and prosolin) is a recently
identified regulator of microtubule (MT) dynamics.
Op18 is a target for both cell cycle and cell surface receptor-coupled kinase systems, and phosphorylation of
Op18 on specific combinations of sites has been shown
to switch off its MT-destabilizing activity. Here we
show that induced expression of the catalytic subunit of
cAMP-dependent protein kinase (PKA) results in a
dramatic increase in cellular MT polymer content concomitant with phosphorylation and partial degradation
of Op18. That PKA may regulate the MT system by
downregulation of Op18 activity was evaluated by a genetic system allowing conditional co-expression of
PKA and a series of kinase target site-deficient mutants of Op18. The results show that phosphorylation of
Op18 on two specific sites, Ser-16 and Ser-63, is necessary and sufficient for PKA to switch off Op18 activity
in intact cells. The regulatory importance of dual phosphorylation on Ser-16 and Ser-63 of Op18 was reproduced by in vitro assays. These results suggest a simple model where PKA phosphorylation downregulates the
MT-destabilizing activity of Op18, which in turn promotes increased tubulin polymerization. Hence, the
present study shows that Op18 has the potential to regulate the MT system in response to external signals
such as cAMP-linked agonists.
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