Thomson R B, Igarashi P, Biemesderfer D, Kim R, Abu-Alfa A, Soleimani M, Aronson P S
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Biol Chem. 1995 Jul 21;270(29):17594-601. doi: 10.1074/jbc.270.29.17594.
Cadherins are recognized as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. We report here the identification of a structurally unique, kidney-specific member of the cadherin multigene family (Ksp-cadherin). cDNA cloning and molecular analysis of the 130-kDa protein confirmed that it was novel and indicated that it most closely resembled members of the LI-cadherin/HPT-1 cadherin subgroup. The predicted protein possesses the definitive cadherin-specific sequence motifs LDRE, DXND, and DXD in well conserved sequential arrangement, and the characteristic cysteine residues found in the last ectodomains of almost all known cadherins. Like LI-cadherin and HPT-1, Ksp-cadherin lacks the prosequence and HAV adhesion recognition sequence typical of most classical cadherins, and possesses a truncated cytoplasmic domain (18-22 amino acids). When expressed in a transient Vaccinia/T7 expression system, Ksp-cadherin displayed the classic calcium sensitivity to trypsin proteolysis that is observed in all cadherins. Immunolocalization studies and Northern analysis indicated that expression of Ksp-cadherin was kidney-specific and limited to the basolateral membranes of renal tubular epithelial cells. In summary, we have identified and cloned a novel, kidney-specific member of the cadherin multigene family that we propose be designated Ksp-cadherin.
钙黏蛋白被认为是同型细胞识别的主要介质，并在组织发育的形态发生方向上发挥着已被证实的作用。我们在此报告鉴定出一种结构独特的、肾脏特异性的钙黏蛋白多基因家族成员（Ksp-钙黏蛋白）。对这种130 kDa蛋白进行的cDNA克隆和分子分析证实它是新发现的，并表明它与LI-钙黏蛋白/HPT-1钙黏蛋白亚组成员最为相似。预测的蛋白具有明确的钙黏蛋白特异性序列基序LDRE、DXND和DXD，且排列顺序保守，还具有几乎所有已知钙黏蛋白在最后一个胞外结构域中发现的特征性半胱氨酸残基。与LI-钙黏蛋白和HPT-1一样，Ksp-钙黏蛋白缺乏大多数经典钙黏蛋白典型的前导序列和HAV黏附识别序列，并且具有截短的胞质结构域（18 - 22个氨基酸）。当在瞬时痘苗病毒/T7表达系统中表达时，Ksp-钙黏蛋白对胰蛋白酶消化表现出所有钙黏蛋白中都观察到的典型钙敏感性。免疫定位研究和Northern分析表明，Ksp-钙黏蛋白的表达具有肾脏特异性，且仅限于肾小管上皮细胞的基底外侧膜。总之，我们已经鉴定并克隆了一种新的、肾脏特异性的钙黏蛋白多基因家族成员，我们建议将其命名为Ksp-钙黏蛋白。
