Beschreibung:
<jats:p>T‐cell immunoglobulin and mucin domain (<jats:styled-content style="fixed-case">TIM</jats:styled-content>)‐2 is expressed on activated B cells. Here, we provide evidence that murine <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 is a target of <jats:styled-content style="fixed-case">ADAM</jats:styled-content>10‐mediated ectodomain shedding, resulting in the generation of a soluble form of <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2. We identified <jats:styled-content style="fixed-case">ADAM</jats:styled-content>10 but not <jats:styled-content style="fixed-case">ADAM</jats:styled-content>17 as the major sheddase of <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2, as shown by pharmacological <jats:styled-content style="fixed-case">ADAM</jats:styled-content>10 inhibition and with <jats:styled-content style="fixed-case">ADAM</jats:styled-content>10‐deficient and <jats:styled-content style="fixed-case">ADAM</jats:styled-content>17‐deficient murine embryonic fibroblasts. Ionomycin‐induced or 2′(3′)‐<jats:italic>O</jats:italic>‐(4‐benzoylbenzoyl) <jats:styled-content style="fixed-case">ATP</jats:styled-content> triethylammonium salt‐induced shedding of <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 was abrogated by deletion of 10 juxtamembrane amino acids from the stalk region but not by deletion of two further N‐terminally located blocks of 10 amino acids, indicating a membrane‐proximal cleavage site. <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 lacking the intracellular domain was cleaved after ionomycin or 2′ (3′)‐<jats:italic>O</jats:italic>‐(4‐benzoylbenzoyl) <jats:styled-content style="fixed-case">ATP</jats:styled-content> triethylammonium salt treatment, indicating that this domain was not involved in the regulation of ectodomain shedding. Moreover, <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 shedding was negatively controlled by calmodulin. Shed and soluble <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 interacted with H‐ferritin. In summary, we describe <jats:styled-content style="fixed-case">TIM</jats:styled-content>‐2 as a novel target for <jats:styled-content style="fixed-case">ADAM</jats:styled-content>10‐mediated ectodomain shedding, and reveal the involvement of <jats:styled-content style="fixed-case">ADAM</jats:styled-content> proteases in cellular iron homeostasis.</jats:p>