ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3

Author(s): Mochizuki S, Shimoda M, Shiomi T, Fujii Y, Okada Y

Source: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 315 (1): 79-84 FEB 27 2004

Abstract: ADAM28, a member of a disintegrin and metalloproteinase (ADAM) family, has two isoforms, membrane-type form (ADAM28m) and secreted form (ADAM28s). Although ADAM28 is expressed and synthesized in a precursor form (proADAM28) by lymphocytes and some cancer cells, its activation mechanism and substrates remain unclear. Here, we report that proADAM28s of 65 kDa is processed with active matrix metalloproteinase-7 (MMP-7) to 42- and 40-kDa forms which corresponds to active ADAM28s without propeptide. Processed ADAM28s digested insulin-like growth factor binding protein-3 (IGFBP-3) in both free and complex forms with IGF-I or IGF-II, and the digestion was prevented with EDTA, 1,10-phenanthroline, KB-R7785, tissue inhibitor of metalloproteinases-3 (TIMP-3), and TIMP-4. These data provide the first evidence that proADAM28s is activated by MMP-7 and ADAM28 digests IGFBP-3.

[摘要] ADAM28被MMP-7所激活并裂解IGFBP-3

ADAM28是金属蛋白酶解离素家族的一个成员，含有两个亚型，膜型(ADAM28m)和分泌型(ADAM28s)。虽然ADAM28在淋巴细胞和癌细胞中表达并以前体细胞的形式被合成，但其活化机制和原理仍不清楚。这里我们报道的65 kDa的前导分泌型ADAM28通过活化的金属基质蛋白酶7(MMP-7)处理成42和40-kDa两亚型，与无前导肽的活化分泌型ADAM28相符合。经处理加工的分泌型ADAM28经胰岛素生长因子I（IGF-I）或胰岛素生长因子II（IGF-II）以单独和复合的形式裂解胰岛素生长因子结合蛋白3(IGFBP-3)，裂解产物经EDTA,，1,10-phenanthroline, KB-R7785, 金属蛋白酶3的组织抑制剂(TIMP-3)以及TIMP-4加以修饰。本文提供的第一手资料证明前导分泌型ADAM28被MMP-7所激活，ADAM28裂解IGFBP-3。

关键词：ADAM28，基质金属蛋白酶7（MMP-7），IGFBP-3，胰岛素样生长因子，TIMP-3