Serra-Pagès C, Medley Q G, Tang M, Hart A, Streuli M
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
J Biol Chem. 1998 Jun 19;273(25):15611-20. doi: 10.1074/jbc.273.25.15611.
LAR family transmembrane protein-tyrosine phosphatases function in axon guidance and mammary gland development. In cultured cells, LAR binds to the intracellular, coiled coil LAR-interacting protein at discrete ends of focal adhesions, implicating these proteins in the regulation of cell-matrix interactions. We describe seven LAR-interacting protein-like genes in humans and Caenorhabditis elegans that form the liprin gene family. Based on sequence similarities and binding characteristics, liprins are subdivided into alpha-type and beta-type liprins. The C-terminal, non-coiled coil regions of alpha-liprins bind to the membrane-distal phosphatase domains of LAR family members, as well as to the C-terminal, non-coiled coil region of beta-liprins. Both alpha- and beta-liprins homodimerize via their N-terminal, coiled coil regions. Liprins are thus multivalent proteins that potentially form complex structures. Some liprins have broad mRNA tissue distributions, whereas others are predominately expressed in the brain. Co-expression studies indicate that liprin-alpha2 alters LAR cellular localization and induces LAR clustering. We propose that liprins function to localize LAR family tyrosine phosphatases at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.
LAR家族跨膜蛋白酪氨酸磷酸酶在轴突导向和乳腺发育中发挥作用。在培养细胞中，LAR在粘着斑的离散末端与细胞内的卷曲螺旋LAR相互作用蛋白结合，表明这些蛋白参与细胞-基质相互作用的调节。我们在人类和秀丽隐杆线虫中描述了七个形成liprin基因家族的LAR相互作用蛋白样基因。根据序列相似性和结合特性，liprin可细分为α型和β型liprin。α-liprin的C末端非卷曲螺旋区域与LAR家族成员的膜远端磷酸酶结构域以及β-liprin的C末端非卷曲螺旋区域结合。α-liprin和β-liprin都通过其N末端卷曲螺旋区域形成同二聚体。因此，liprin是潜在形成复杂结构的多价蛋白。一些liprin具有广泛的mRNA组织分布，而另一些则主要在大脑中表达。共表达研究表明，liprin-α2改变LAR的细胞定位并诱导LAR聚集。我们提出，liprin的功能是将LAR家族酪氨酸磷酸酶定位在质膜上的特定位点，可能调节它们与细胞外环境的相互作用以及与底物的结合。
