Soluble T cell immunoglobulin and mucin domain (TIM)-1 and -4 generated by A Disintegrin And Metalloprotease (ADAM)-10 and -17 bind to phosphatidylserine

详细信息    查看全文

• 作者：Olga Schweigert ; Christin Dewitz ; Katja M枚ller-Hackbarth ; Ahmad Trad ; Christoph Garbers ; Stefan Rose-John ; J眉rgen Scheller
• 关键词：DMEM ; Dulbecco's modified Eagle's medium ; FBS ; fetal bovine serum ; mAb ; monoclonal antibody
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：February, 2014
• 年：2014
• 卷：1843
• 期：2
• 页码：275-287
• 全文大小：887 K

文摘

T cell immunoglobulin and mucin domain 1 and 4 (TIM-1 and -4) proteins serve as phosphatidylserine receptors to engulf apoptotic cells. Here we show that human TIM-1 and TIM-4 proteins are targets of A Disintegrin And Metalloprotease (ADAM)-mediated ectodomain shedding resulting in soluble forms of TIM-1 and TIM-4. We identified ADAM10 and ADAM17 as major sheddases of TIM-1 and TIM-4 as shown by protease-specific inhibitors, the ADAM10 prodomain, siRNA and ADAM10/ADAM17 deficient murine embryonic fibroblasts (MEFs). TIM-1 and TIM-4 lacking the intracellular domain were efficiently cleaved after ionomycin- and PMA-treatment, indicating that the intracellular domain was not necessary for ectodomain shedding. Soluble TIM-1 and -4 were able to bind to phosphatidylserine, suggesting that soluble TIM-1 and -4 might act as negative regulators of cellular TIM-1 and -4. In summary, we describe TIM-1 and TIM-4 as novel targets for ADAM10- and ADAM17-mediated ectodomain shedding.