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

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Molecular cell (Impact Factor: 14.02). 03/2011; 41(6):661-71. DOI: 10.1016/j.molcel.2011.02.031
Source: PubMed


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.

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Available from: Michelle C Mendoza
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    • "The Ras-ERK1/2 MAP kinase pathway plays a critical role in numerous cellular processes, including proliferation, differentiation, survival, and motility [20]. Growth factors activate ERK-MAPK by signaling through their cognate receptors at the cell surface to the small GTPase Ras. "
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