Mol Cell. 2011 Mar 18;41(6):661-71. doi: 10.1016/j.molcel.2011.02.031.

ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex.

Mendoza MC, Er EE, Zhang W, Ballif BA, Elliott HL, Danuser G, Blenis J.

Source

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. michelle_mendoza@hms.harvard.edu

Abstract

Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal-regulated kinase-mitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate that ERK controls protrusion initiation and protrusion speed. Lamellipodial protrusions are generated via the WRC (WAVE2 regulatory complex), which activates the Arp2/3 actin nucleator for actin assembly. The WRC must be phosphorylated to be activated, but the sites and kinases that regulate its intermolecular changes and membrane recruitment are unknown. We show that ERK colocalizes with the WRC at lamellipodial leading edges and directly phosphorylates two WRC components: WAVE2 and Abi1. The phosphorylations are required for functional WRC interaction with Arp2/3 and actin during cell protrusion. Thus, ERK coordinates adhesion disassembly with WRC activation and actin polymerization to promote productive leading edge advancement during cell migration.