Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cells. 2021 Apr 7;10(4):825. doi: 10.3390/cells10040825.
Integrins serve as conduits for the transmission of information between cells and their extracellular environment. Signaling across integrins is bidirectional, transducing both inside-out and outside-signaling. Integrin activation, a transition from a low affinity/avidity state to a high affinity/avidity state for cognate ligands, is an outcome of inside-signaling. Such activation is particularly important for the recognition of soluble ligands by blood cells but also influences cell-cell and cell-matrix interactions. Integrin activation depends on a complex series of interactions, which both accelerate and inhibit their interconversion from the low to the high affinity/avidity state. There are three components regarded as being most proximately involved in integrin activation: the integrin cytoplasmic tails, talins and kindlins. The participation of each of these molecules in integrin activation is highly regulated by post-translation modifications. The importance of targeted phosphorylation of integrin cytoplasmic tails and talins in integrin activation is well-established, but much less is known about the role of post-translational modification of kindlins. The kindlins, a three-member family of 4.1-ezrin-radixin-moesin (FERM)-domain proteins in mammals, bind directly to the cytoplasmic tails of integrin beta subunits. This commentary provides a synopsis of the emerging evidence for the role of kindlin phosphorylation in integrin regulation.
整合素作为细胞与其细胞外环境之间信息传递的通道。整合素信号传递是双向的，既能传递内部信号，也能传递外部信号。整合素的激活是从低亲和力/亲合力状态向高亲和力/亲合力状态转变的结果，是内部信号传递的结果。这种激活对于血细胞识别可溶性配体尤为重要，但也影响细胞-细胞和细胞-基质的相互作用。整合素的激活取决于一系列复杂的相互作用，这些相互作用既加速了它们从低亲和力/亲合力状态向高亲和力/亲合力状态的转换，也抑制了这种转换。有三个被认为最直接参与整合素激活的组件：整合素胞质尾部、talin 和 kindlin。这些分子中每一个在整合素激活中的参与都受到高度的翻译后修饰调控。整合素胞质尾部和 talin 的靶向磷酸化在整合素激活中的重要性已得到充分证实，但关于 kindlin 翻译后修饰作用的了解要少得多。Kindlin 是哺乳动物中一个由三个成员组成的 4.1-埃兹蛋白（ezrin）-radixin-moesin（radixin）-膜突蛋白（moesin，FERM）结构域蛋白家族，直接与整合素β亚基的胞质尾部结合。本评论简要介绍了 kindlin 磷酸化在整合素调节中的作用的新证据。
