Phosphoregulation of the WAVE regulatory complex and signal integration.

Phosphoregulation of the WAVE regulatory complex and signal integration.
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DOI:
10.1016/j.semcdb.2013.01.007
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发表时间:
2013-04
影响因子:
7.3
通讯作者:
Mendoza, Michelle C.
Mendoza, Michelle C.
中科院分区:
生物学2区
文献类型:
--
作者:
Mendoza, Michelle C.

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WAVE2调控复合体(WRC)通过激活肌动蛋白核转录因子Arp2/3诱导肌动蛋白聚合,使肌动蛋白聚合作用于细胞膜,导致细胞边缘突起。为了正确控制这种细胞形态和功能的变化,细胞进化出多种方法,在空间和时间上密切调控WRC和Arp2/3的活性。在这些机制中,磷酸化在向WRC和肌动蛋白细胞骨架传递细胞外和细胞内信号方面起着重要作用。这篇综述讨论了基于磷酸化的调控输入到WRC。对生长因子、趋化因子、激素和细胞外基质作出反应的信号通路汇聚在WRC的Wave和ABI组件上。Abl、Src、ERK和PKA激酶通过WRC构象变化促进复合体激活,WRC构象变化允许与Arp2/3复合体相互作用,并通过WRC移位到细胞边缘。神经元特异性的CDK5和固有活性的CK2激酶抑制WRC的激活。这些调控信号在空间和时间上被整合,因为它们结合在WRC上。WRC磷酸化事件和WRC活性的组合受刺激、细胞类型和细胞周期特异性途径激活以及途径交叉抑制和交叉激活的控制。
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.
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