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Phosphoregulation of the WAVE regulatory complex and signal integration

[Display omitted] ► Abl, Src, ERK, CDKs, and CK2 phosphorylate WAVE and ABI at unique sites. ► Extracellular stimuli activate Abl and ERK to phosphorylate and activate the WRC. ► The constitutively active CK2 phosphorylates WAVE to inhibit WRC activity. ► In neurons, CDK5 phosphorylates WAVE and inh...

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Published in:Seminars in cell & developmental biology 2013-04, Vol.24 (4), p.272-279
Main Author: Mendoza, Michelle C.
Format: Article
Language:English
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Summary:[Display omitted] ► Abl, Src, ERK, CDKs, and CK2 phosphorylate WAVE and ABI at unique sites. ► Extracellular stimuli activate Abl and ERK to phosphorylate and activate the WRC. ► The constitutively active CK2 phosphorylates WAVE to inhibit WRC activity. ► In neurons, CDK5 phosphorylates WAVE and inhibits WRC activity. ► PKA activates a phosphatase to remove the inhibitory CDK5 phosphorylations. The WAVE2 regulatory complex (WRC) induces actin polymerization by activating the actin nucleator Arp2/3. Polymerizing actin pushes against the cell membrane and induces dramatic edge protrusions. In order to properly control such changes in cell morphology and function, cells have evolved multiple methods to tightly regulate WRC and Arp2/3 activity in space and time. Of these mechanisms, phosphorylation plays a fundamental role in transmitting extracellular and intracellular signals to the WRC and the actin cytoskeleton. This review discusses the phosphorylation-based regulatory inputs into the WRC. Signaling pathways that respond to growth factors, chemokines, hormones, and extracellular matrix converge upon the WAVE and ABI components of the WRC. The Abl, Src, ERK, and PKA kinases promote complex activation through a WRC conformation change that permits interaction with the Arp2/3 complex and through WRC translocation to the cell edge. The neuron-specific CDK5 and constitutively active CK2 kinases inhibit WRC activation. These regulatory signals are integrated in space and time as they coalesce upon the WRC. The combination of WRC phosphorylation events and WRC activity is controlled by stimulus, cell type, and cell cycle-specific pathway activation and via pathway cross-inhibition and cross-activation.
ISSN:1084-9521
1096-3634
DOI:10.1016/j.semcdb.2013.01.007