Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth.
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.
Irwin
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N
Department of Neurosurgery, Children's Hospital, Boston, MA 02115, USA. nina.irwin@childrens.harvard.edu
Li
Y-M
YM
O'Toole
J E
JE
Benowitz
L I
LI
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000201:enzymology*; D002417:Cattle; D002525:Cerebellar Cortex / Q000166:cytology / Q000201:enzymology; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016501:Neurites / Q000201:enzymology*; D016716:PC12 Cells; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
D007527:Isoenzymes; D011494:Protein Kinases