Rosen A, Keenan K F, Thelen M, Nairn A C, Aderem A
Rockefeller University, New York, NY 10021.
J Exp Med. 1990 Oct 1;172(4):1211-5. doi: 10.1084/jem.172.4.1211.
The myristoylated, alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells, and has been implicated in diverse cellular processes including neurosecretion, fibroblast mitogenesis, and macrophage activation. In macrophages that have spread on the substratum, MARCKS has a punctate distribution at the cell-substratum interface of pseudopodia and filopodia. At these points, MARCKS co-localizes with vinculin and talin. Activation of PKC with phorbol esters results in the rapid disappearance of punctate staining of MARCKS, but not vinculin or talin, and is accompanied by cell spreading and loss of filopodia. The morphological changes and disappearance of punctate staining follow a time-course that closely approximates both the PKC-dependent phosphorylation of MARCKS, and its phosphorylation-dependent release from the plasma membrane. Our results suggest a role for PKC-dependent phosphorylation of MARCKS in the regulation of the membrane cytoskeleton.
豆蔻酰化富含丙氨酸的蛋白激酶C底物(MARCKS)是多种细胞中蛋白激酶C(PKC)的主要底物,并且参与了包括神经分泌、成纤维细胞有丝分裂和巨噬细胞激活在内的多种细胞过程。在铺展于基质上的巨噬细胞中,MARCKS在伪足和丝状伪足的细胞-基质界面呈点状分布。在这些部位,MARCKS与纽蛋白和踝蛋白共定位。用佛波酯激活PKC会导致MARCKS点状染色迅速消失,但纽蛋白或踝蛋白不受影响,同时伴随着细胞铺展和丝状伪足消失。形态学变化和点状染色消失的时间进程与MARCKS依赖PKC的磷酸化及其从质膜的磷酸化依赖性释放密切相关。我们的数据表明,MARCKS依赖PKC的磷酸化在膜细胞骨架的调节中发挥作用。