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T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding

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T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding. / Dewitz, Christin; Möller-Hackbarth, Katja; Schweigert, Olga; Reiss, Karina; Chalaris, Athena; Scheller, Jürgen; Rose-John, Stefan.

In: FEBS J, Vol. 281, No. 1, 01.2014, p. 157-74.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dewitz, C, Möller-Hackbarth, K, Schweigert, O, Reiss, K, Chalaris, A, Scheller, J & Rose-John, S 2014, 'T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding', FEBS J, vol. 281, no. 1, pp. 157-74. https://doi.org/10.1111/febs.12583

APA

Dewitz, C., Möller-Hackbarth, K., Schweigert, O., Reiss, K., Chalaris, A., Scheller, J., & Rose-John, S. (2014). T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding. FEBS J, 281(1), 157-74. https://doi.org/10.1111/febs.12583

Vancouver

Dewitz C, Möller-Hackbarth K, Schweigert O, Reiss K, Chalaris A, Scheller J et al. T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding. FEBS J. 2014 Jan;281(1):157-74. https://doi.org/10.1111/febs.12583

Bibtex

@article{3e1ffbab77f447819a41316d959cdf80,
title = "T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding",
abstract = "T-cell immunoglobulin and mucin domain (TIM)-2 is expressed on activated B cells. Here, we provide evidence that murine TIM-2 is a target of ADAM10-mediated ectodomain shedding, resulting in the generation of a soluble form of TIM-2. We identified ADAM10 but not ADAM17 as the major sheddase of TIM-2, as shown by pharmacological ADAM10 inhibition and with ADAM10-deficient and ADAM17-deficient murine embryonic fibroblasts. Ionomycin-induced or 2'(3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt-induced shedding of TIM-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. TIM-2 lacking the intracellular domain was cleaved after ionomycin or 2' (3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt treatment, indicating that this domain was not involved in the regulation of ectodomain shedding. Moreover, TIM-2 shedding was negatively controlled by calmodulin. Shed and soluble TIM-2 interacted with H-ferritin. In summary, we describe TIM-2 as a novel target for ADAM10-mediated ectodomain shedding, and reveal the involvement of ADAM proteases in cellular iron homeostasis. ",
keywords = "ADAM Proteins/genetics, ADAM10 Protein, Amyloid Precursor Protein Secretases/genetics, Animals, Apoferritins/metabolism, B-Lymphocytes/cytology, Blotting, Western, COS Cells, Calmodulin/antagonists & inhibitors, Cell Membrane/metabolism, Cell Proliferation, Cells, Cultured, Chlorocebus aethiops, Flow Cytometry, HEK293 Cells, Humans, Immunoprecipitation, Ionomycin/pharmacology, Male, Membrane Proteins/genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mutation/genetics",
author = "Christin Dewitz and Katja M{\"o}ller-Hackbarth and Olga Schweigert and Karina Reiss and Athena Chalaris and J{\"u}rgen Scheller and Stefan Rose-John",
note = "{\textcopyright} 2013 FEBS.",
year = "2014",
month = jan,
doi = "10.1111/febs.12583",
language = "English",
volume = "281",
pages = "157--74",
journal = "FEBS J",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - T-cell immunoglobulin and mucin domain 2 (TIM-2) is a target of ADAM10-mediated ectodomain shedding

AU - Dewitz, Christin

AU - Möller-Hackbarth, Katja

AU - Schweigert, Olga

AU - Reiss, Karina

AU - Chalaris, Athena

AU - Scheller, Jürgen

AU - Rose-John, Stefan

N1 - © 2013 FEBS.

PY - 2014/1

Y1 - 2014/1

N2 - T-cell immunoglobulin and mucin domain (TIM)-2 is expressed on activated B cells. Here, we provide evidence that murine TIM-2 is a target of ADAM10-mediated ectodomain shedding, resulting in the generation of a soluble form of TIM-2. We identified ADAM10 but not ADAM17 as the major sheddase of TIM-2, as shown by pharmacological ADAM10 inhibition and with ADAM10-deficient and ADAM17-deficient murine embryonic fibroblasts. Ionomycin-induced or 2'(3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt-induced shedding of TIM-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. TIM-2 lacking the intracellular domain was cleaved after ionomycin or 2' (3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt treatment, indicating that this domain was not involved in the regulation of ectodomain shedding. Moreover, TIM-2 shedding was negatively controlled by calmodulin. Shed and soluble TIM-2 interacted with H-ferritin. In summary, we describe TIM-2 as a novel target for ADAM10-mediated ectodomain shedding, and reveal the involvement of ADAM proteases in cellular iron homeostasis.

AB - T-cell immunoglobulin and mucin domain (TIM)-2 is expressed on activated B cells. Here, we provide evidence that murine TIM-2 is a target of ADAM10-mediated ectodomain shedding, resulting in the generation of a soluble form of TIM-2. We identified ADAM10 but not ADAM17 as the major sheddase of TIM-2, as shown by pharmacological ADAM10 inhibition and with ADAM10-deficient and ADAM17-deficient murine embryonic fibroblasts. Ionomycin-induced or 2'(3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt-induced shedding of TIM-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. TIM-2 lacking the intracellular domain was cleaved after ionomycin or 2' (3')-O-(4-benzoylbenzoyl) ATP triethylammonium salt treatment, indicating that this domain was not involved in the regulation of ectodomain shedding. Moreover, TIM-2 shedding was negatively controlled by calmodulin. Shed and soluble TIM-2 interacted with H-ferritin. In summary, we describe TIM-2 as a novel target for ADAM10-mediated ectodomain shedding, and reveal the involvement of ADAM proteases in cellular iron homeostasis.

KW - ADAM Proteins/genetics

KW - ADAM10 Protein

KW - Amyloid Precursor Protein Secretases/genetics

KW - Animals

KW - Apoferritins/metabolism

KW - B-Lymphocytes/cytology

KW - Blotting, Western

KW - COS Cells

KW - Calmodulin/antagonists & inhibitors

KW - Cell Membrane/metabolism

KW - Cell Proliferation

KW - Cells, Cultured

KW - Chlorocebus aethiops

KW - Flow Cytometry

KW - HEK293 Cells

KW - Humans

KW - Immunoprecipitation

KW - Ionomycin/pharmacology

KW - Male

KW - Membrane Proteins/genetics

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mutation/genetics

U2 - 10.1111/febs.12583

DO - 10.1111/febs.12583

M3 - SCORING: Journal article

C2 - 24164679

VL - 281

SP - 157

EP - 174

JO - FEBS J

JF - FEBS J

SN - 1742-464X

IS - 1

ER -