Liliental J, Chang D D
Department of Medicine, Microbiology and Immunology, University of California at Los Angeles School of Medicine 90095, USA.
J Biol Chem. 1998 Jan 23;273(4):2379-83. doi: 10.1074/jbc.273.4.2379.
The integrin beta subunit cytoplasmic domains are important for activation-dependent cell adhesion and adhesion-dependent signaling events. We report an interaction between integrin beta subunit cytoplasmic domain and Rack1, a Trp-Asp (WD) repeat protein that has been shown to bind activated protein kinase C. The Rack1-binding site on integrin beta 2 subunit resides within a conserved, membrane-proximal region. In the yeast two-hybrid assay, WD repeats five to seven of Rack1 (Rack1-WD5/7) interact with integrin beta 1, beta 2, and beta 5 cytoplasmic domain. In eukaryotic cells, Rack1 co-immunoprecipitates with at least two different beta integrins, beta 1 integrins in 293T cells and beta 2 integrins in JY lymphoblastoid cells. Whereas Rack1-WD5/7 binds integrins constitutively, the association of full-length Rack1 to integrins in vivo requires a treatment with phorbol esters, which promotes cell spreading and adhesion. These findings suggest that Rack1 may link protein kinase C directly to integrins and participate in the regulation of integrin functions.
整合素β亚基的胞质结构域对于依赖激活的细胞黏附以及依赖黏附的信号转导事件很重要。我们报道了整合素β亚基胞质结构域与Rack1之间的相互作用，Rack1是一种色氨酸-天冬氨酸（WD）重复蛋白，已被证明可结合活化的蛋白激酶C。整合素β2亚基上的Rack1结合位点位于一个保守的、靠近膜的区域内。在酵母双杂交实验中，Rack1的WD重复序列5至7（Rack1-WD5/7）与整合素β1、β2和β5的胞质结构域相互作用。在真核细胞中，Rack1与至少两种不同的β整合素共免疫沉淀，在293T细胞中与β1整合素，在JY淋巴母细胞中与β2整合素。虽然Rack1-WD5/7组成性地结合整合素，但全长Rack1在体内与整合素的结合需要用佛波酯处理，这会促进细胞铺展和黏附。这些发现表明，Rack1可能将蛋白激酶C直接与整合素联系起来，并参与整合素功能的调节。
