猫白血球由来5アミノ酸残基欠失肝細胞増殖因子cDNAの単離および発現 Isolation and Expression of Five-Amino-Acid-Deleted Variant of Feline Hepatocyte Growth Factor (HGF) cDNA

肝細胞増殖因子(HGF)は,多彩な生物活性を有するサイトカインであり,肝細胞,上皮細胞,色素細胞,内皮細胞および造血細胞など多岐にわたる細胞に作用する。我々は,猫白血球由来cDNAから第1クリングルドメイン内の5アミノ酸残基が欠失するスプライスバリアントHGFを単離した。次に,5アミノ酸残基欠失猫HGFおよび猫HGFの生物活性を比較するため,哺乳動物細胞発現ベクターを構築し,COS-7細胞に遺伝子導入した。得られた組換え5アミノ酸残基欠失猫HGFおよび猫HGFは,マウス肝由来細胞株であるBNL CL.2細胞の増殖を刺激し,さらにMDCK細胞の遊走性を充進した。5アミノ酸残基欠失猫HGFは,細胞増殖および遊走において,猫HGFと同等の活性を有することが示された。

Hepatocyte growth factor (HGF) is a pleiotropic cytokine that stimulates a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial and hematopoietic cells. We have cloned a different form of cDNA, with a deletion of 15 base pairs predicted to result in the loss of 5 amino acids from the first kringle domain. To investigate the biological activity, original and deleted variant of feline HGF cDNAs were transiently expressed in COS-7 cells. Both recombinant feline HGFs showed almost the same dose-response curves in the stimulation of the growth of BNL CL.2 cells (a mouse hepatocyte cell line) and scatter activity of Madin-Darby canine kidney (MDCK) cells. The findings reported here suggest that the deleted variant of feline HGF has almost the same biological activity as the original in terms of the proliferation and scatter activity.