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

doi:10.1073/pnas.0605135103

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

*Department of Neurosurgery and
^†Neurobiology Program, Children's Hospital, Boston, MA 02115; and
^‡Department of Surgery and
^¶Program in Neuroscience, Harvard Medical School, Boston, MA 02115

Edited by Yuh Nung Jan, University of California School of Medicine, San Francisco, CA, and approved October 13, 2006 (received for review June 19, 2006)

Abstract

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.

Footnotes

^§To whom correspondence may be addressed. E-mail: larry.benowitz{at}childrens.harvard.edu or nina.Irwin{at}childrens.harvard.edu
Author contributions: N.I. and L.I.B. designed research; N.I., Y.-M.L., and J.E.O. performed research; N.I. and L.I.B. analyzed data; and N.I. and L.I.B. wrote the paper.
Conflict of interest statement: L.I.B. is a paid consultant to Boston Life Sciences, which also provides partial funding to the laboratory.
This article is a PNAS direct submission.
Abbreviations:

6-TG,

6-thioguanine;

IP,

immunoprecipitation;

NGF,

nerve growth factor;

shRNA,

small hairpin RNA.