Autoactivation of prolegumain is accelerated by glycosaminoglycans

作者：Berven Lise; Johansen Harald Thidemann; Solberg Rigmor; Kolset Svein Olav; Samuelsen Anne Bent C^*

来源：Biochimie, 2013, 95(4): 772-781.

DOI：10.1016/j.biochi.2012.11.002

• Legumain
• Glycosaminoglycan
• Chondroitin sulphate
• Heparin
• Heparan sulphate

The cysteine protease legumain participates in several biological and pathological processes including tumour invasion and metastasis. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform in order to reach an enzymatically active form. Here we demonstrate that the naturally occurring polyanionic glycosaminoglycans (GAGs) chondroitin 4-sulphate (C4S), chondroitin 6-sulphate (C6S), chondroitin 4,6-sulphate (C4,6S), heparin, heparan sulphate (HS) as well as chondroitin sulphate (CS)-derived decasaccharides accelerated the autocatalytic activation of prolegumain through ionic interactions in a concentration-, size- and time-dependent manner at pH 4.0. In contrast, at pH 5.0 only C4S and C4,6S were able to promote prolegumain activation, while CS-derived decasaccharides, C6S, heparin and HS lost their effect at this pH.

• 出版日期2013-4