Mori Tsuyoshi, Moriuchi Ryozo, Okazaki Eiko, Yamada Kenji, Katamine Shigeru
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Biochem Biophys Res Commun. 2007 Apr 20;355(4):937-43. doi: 10.1016/j.bbrc.2007.02.051. Epub 2007 Feb 20.
We identified RECK, a membrane-anchored glycoprotein negatively regulating the activities of MMPs, as a molecule interacting with Tgat oncoprotein consisting of RhoGEF domain and the unique C-terminal 15 amino acids. The Tgat increased the invasive potential of NIH3T3 cells expressing endogenous mouse RECK and this effect was partially inhibited by the co-expression of human RECK. On the contrary, the expression of exogenous human RECK in HT1080 cell line lacking the endogenous RECK expression reduced its invasive activity, which was recovered by the Tgat co-expression. Moreover, a Tgat mutant lacking the C-terminal region lost the potential to compete the function of RECK in HT1080 cells. These findings indicate that Tgat is the functional inhibitor of RECK, and the activation of MMPs induced by Tgat is likely to enhance invasive activities of cancer cells expressing Tgat.
我们鉴定出RECK，一种对基质金属蛋白酶（MMPs）活性具有负调控作用的膜锚定糖蛋白，它是一种与由RhoGEF结构域和独特的C末端15个氨基酸组成的Tgat癌蛋白相互作用的分子。Tgat增加了表达内源性小鼠RECK的NIH3T3细胞的侵袭潜能，而人RECK的共表达可部分抑制这种作用。相反，在缺乏内源性RECK表达的HT1080细胞系中外源人RECK的表达降低了其侵袭活性，而Tgat的共表达可使其恢复。此外，缺失C末端区域的Tgat突变体失去了在HT1080细胞中竞争RECK功能的潜能。这些发现表明Tgat是RECK的功能抑制剂，并且Tgat诱导的MMPs激活可能增强表达Tgat的癌细胞的侵袭活性。
