Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity

Abstract

Summary The WAVE family of proteins has long been implicated in the stimulus-dependent generation of lamellipodia at the leading edge of migrating cells, with WAVE2 in particular implicated in the formation of peripheral ruffles and chemotactic migration. However, the lack of direct visualisation of cell migration in WAVE2 mutants or knockdowns has made defining the mechanisms of WAVE2 regulation during cell migration difficult. We have characterised three MAP kinase phosphorylation sites within WAVE2 and analysed fibroblast behaviour in a scratch-wound model following introduction of transgenes encoding phospho-defective WAVE2. The cells exhibited an increase in migration speed, a decrease in the persistence of migration, and disruption of polarisation of the Golgi apparatus. All these effects could be mimicked by acute knockdown of endogenous WAVE2 expression with RNAi, indicating that phosphorylation of WAVE2 by MAP kinases regulates cell polarity during migration.

Cdk5 Phosphorylation of WAVE2 Regulates Oligodendrocyte Precursor Cell Migration through Nonreceptor Tyrosine Kinase Fyn

“…Very recently, it has been reported that other proline-directed kinases, namely, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), phosphorylate WAVE2 at a proline-rich region in response to growth factors, serum stimulation, and scratch wounding in fibroblasts (Danson et al, 2007). These phosphorylation events participate in regulating the establishment of polarity and direction of migration.…”

A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress

“…For lentiviral transduction of erythroid cells (see below), vectors containing 64-105 Atg4D-GFP and DN63 Atg4D-GFP were obtained by sub-cloning into pxlg3-gfp (a modified pSEW sin vector kindly provided by Dr. G. Cory, Exeter University, UK) 45 after removal of GFP from the pxlg3 vector backbone. Lentiviruses were produced by cotransfection of the pxlg3 constructs in HEK 293T cells as described previously.…”

WAVE2 regulates meiotic spindle stability, peripheral positioning and polar body emission in mouse oocytes

“…16,17 WAVE2 participates in multiple processes related to actin dynamics, such as lamellipodia and filopodium formation, 18,19 cell migration and protrusion, [20][21][22] and embryogenesis.…”

“…WAVE2 can be phosphorylated by MAPK 21 and forms a complex with PKA that regulates membrane protrusion. 24 In mouse oocytes, Rac, the activator of WAVE2, is necessary for spindle formation, migration and anchoring during meiosis; 25 however, there is no direct evidence linking oocyte polarization to WAVE2.…”