TY - JOUR
T1 - ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3
AU - Mochizuki, Satsuki
AU - Shimoda, Masayuki
AU - Shiomi, Takayuki
AU - Fujii, Yutaka
AU - Okada, Yasunori
N1 - Funding Information:
We are grateful to Dr. Kazushi Iwata in Daiichi Fine Chemical Co. Ltd. and Dr. Koichiro Yoshino in Carnabiosience for providing us with TIMPs and a synthetic ADAM inhibitor, respectively. This work was supported by the Ministry of Education, Science and Culture of Japan (Grant-in-Aid for scientific research on priority area B2-11240206) to Y.O.
PY - 2004/2/27
Y1 - 2004/2/27
N2 - 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 65kDa 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.
AB - 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 65kDa 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.
KW - ADAM28
KW - Insulin like growth factor
KW - Insulin-like growth factor binding protein-3
KW - MMP-7
KW - TIMP-3
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U2 - 10.1016/j.bbrc.2004.01.022
DO - 10.1016/j.bbrc.2004.01.022
M3 - Article
C2 - 15013428
AN - SCOPUS:0842308119
SN - 0006-291X
VL - 315
SP - 79
EP - 84
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
