Proteomics

Dataset Information

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Degradome of soluble ADAM10 and ADAM17 metalloproteases


ABSTRACT: Disintegrin and metalloproteinases ADAM10 and ADAM17 can release the extracellular region of a variety of membrane-bound proteins including cytokines, adhesion molecules, growth factors and receptors, important for many biological functions (ectodomain shedding).. So far, substrate identification for ADAM10 and ADAM17 focused exclusively on their membrane-anchored forms and their function as sheddases. With ADAM8 we now describe the first protease capable of releasing the ADAM17 ectodomain. Based on these findings, we investigated whether the soluble ectodomains of ADAM10 and ADAM17 still exhibit shedding activity and to determine their soluble protein substrate pool . To address this, a mass spectrometry-based N-terminomics approach (TAILS) was used to identify potential targets of soluble ADAM10 and ADAM17 (sADAM10/17) within the secretome of the murine cardiomyocyte cell line HL-1. We identified almost 140 protein cleavage events in total and 45 common substrates for both sADAM10 and sADAM17. Further in-vitro studies confirmed fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of soluble ADAM10 and/or ADAM17. Overall, we present the first degradome study for sADAM10 and sADAM17, thereby introducing a new regulation mode of the proteolytic activity of these essential proteases within the protease web.

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture, Cardiac Muscle Cell

SUBMITTER: Andreas Tholey  

LAB HEAD: Prof. Andreas Tholey

PROVIDER: PXD013718 | Pride | 2019-06-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
150517_AH_A10A17substrates_mix_A10.raw Raw
150517_AH_A10A17substrates_mix_A17.raw Raw
150517_AH_A10A17substrates_mix_control.raw Raw
260419_AH_C_A10.raw Raw
260419_AH_C_A17.raw Raw
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Publications


Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit  ...[more]

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