LeClaire et al. identify a kinase that helps activate the actin-nucleating Arp2/3 complex.

The Arp2/3 complex spurs membrane protrusion and cell movement by triggering formation of branched actin filaments. WAVE and WASP proteins switch on the Arp2/3 complex, but the complex’s activation also requires phosphorylation of Arp2. However, the kinase responsible for this phosphorylation was unknown.

LeClaire et al. tested several candidates and found that Nck-interacting kinase (NIK, also known as MAP4K4) phosphorylated Arp2 and other subunits of the complex in vitro. It wasn’t the only one, however. Src also phosphorylated the Arp2 and Arp3 subunits. The researchers therefore put the two kinases through a further test by stripping away all phosphate groups from the complex. NIK restored the Arp2/3 complex’s ability to polymerize actin in vitro but Src did not, suggesting that phosphorylation by NIK helps to activate the complex.

The team also gauged NIK’s effects in cells. Epidermal growth factor (EGF) spurs actin assembly in cancer cells. LeClaire et al. discovered that a dominant-negative version of Arp2/3 that can’t be phosphorylated prevented EGF-induced actin polymerization in these cells. Knocking down NIK with shRNA also curbed polymerization and inhibited membrane protrusion.

The researchers suggest that Arp2/3’s two on-switches—WASP/WAVE and phosphorylation of Arp2—serve as a coincidence detector. The Arp2/3 complex remains inactive unless two stimuli arrive within a short time of each other.

, et al
J. Cell Biol.

Author notes

Text by Mitch Leslie