Even-Faitelson Liron, Ravid Shoshana
Department of Biochemistry, Institute of Medical Sciences, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
Mol Biol Cell. 2006 Jul;17(7):2869-81. doi: 10.1091/mbc.e05-11-1001. Epub 2006 Apr 12.
Many signaling pathways regulate the function of the cellular cytoskeleton. Yet we know very little about the proteins involved in the cross-talk between the signaling and the cytoskeletal systems. Here we show that myosin II-B, an important cytoskeletal protein, resides in a complex with p21-activated kinase 1 (PAK1) and atypical protein kinase C (PKC) zeta (aPKCzeta) and that the interaction between these proteins is EGF-dependent. We further show that PAK1 is involved in aPKCzeta phosphorylation and that aPKCzeta phosphorylates myosin II-B directly on a specific serine residue in an EGF-dependent manner. This latter phosphorylation is specific to isoform B of myosin II, and it leads to slower filament assembly of myosin II-B. Furthermore, a decrease in aPKCzeta expression in the cells alters myosin II-B cellular organization. Our finding of a new signaling pathway involving PAK1, aPKCzeta, and myosin II-B, which is implicated in myosin II-B filament assembly and cellular organization, provides an important link between the signaling system and cytoskeletal dynamics.
许多信号通路调节细胞骨架的功能。然而，我们对参与信号系统与细胞骨架系统之间相互作用的蛋白质了解甚少。在此，我们表明肌球蛋白II-B，一种重要的细胞骨架蛋白，与p21激活激酶1（PAK1）和非典型蛋白激酶C（PKC）ζ（aPKCζ）存在于一个复合物中，并且这些蛋白之间的相互作用是表皮生长因子（EGF）依赖性的。我们进一步表明，PAK1参与aPKCζ的磷酸化，并且aPKCζ以EGF依赖性方式直接在特定丝氨酸残基上磷酸化肌球蛋白II-B。后一种磷酸化是肌球蛋白II的B亚型所特有的，并且它导致肌球蛋白II-B的丝状体组装变慢。此外，细胞中aPKCζ表达的降低会改变肌球蛋白II-B的细胞组织。我们发现了一条涉及PAK1、aPKCζ和肌球蛋白II-B的新信号通路，该通路与肌球蛋白II-B的丝状体组装和细胞组织有关，这为信号系统与细胞骨架动力学之间提供了重要联系。
