Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth

N Irwin, YM Li, JE O'toole… - Proceedings of the …, 2006 - National Acad Sciences
N Irwin, YM Li, JE O'toole, LI Benowitz
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
The growth of axons is fundamental to the development and repair of brain circuitry. We
show here that Mst3b, a neuron-specific homolog of the yeast kinase Ste20, is critical for
axon outgrowth. Mst3b is activated in response to trophic factors, and suppressing its
expression (via siRNAs) or its function (by a dominant-negative mutant) blocks axon
outgrowth. Inosine, a purine nucleoside that stimulates axon outgrowth, activates Mst3b
kinase activity, whereas 6-thioguanine, a purine analog that blocks outgrowth, inhibits the …
The growth of axons is fundamental to the development and repair of brain circuitry. We show here that Mst3b, a neuron-specific homolog of the yeast kinase Ste20, is critical for axon outgrowth. Mst3b is activated in response to trophic factors, and suppressing its expression (via siRNAs) or its function (by a dominant-negative mutant) blocks axon outgrowth. Inosine, a purine nucleoside that stimulates axon outgrowth, activates Mst3b kinase activity, whereas 6-thioguanine, a purine analog that blocks outgrowth, inhibits the activity of this kinase. These findings place Mst3b as a key regulator of axon outgrowth and help explain the purine sensitivity of this process.
National Acad Sciences