Involvement of conserved tryptophan residues for secretion of TIMP‑2

Ukaji,Tamami; Sasazawa,Yukiko; Umezawa,Kazuo; Simizu,Siro

doi:10.3892/ol.2013.1771

2014-March Volume 7 Issue 3

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2014-March Volume 7 Issue 3

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Involvement of conserved tryptophan residues for secretion of TIMP‑2

Authors:
- Tamami Ukaji
- Yukiko Sasazawa
- Kazuo Umezawa
- Siro Simizu
View Affiliations / Copyright

Affiliations: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa 223‑8522, Japan
Pages: 631-634
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Published online on: December 23, 2013

https://doi.org/10.3892/ol.2013.1771
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Abstract

Tissue inhibitor of metalloproteinases (TIMPs) are endogenous inhibitor proteins of matrix metalloproteinases and contain 12 cysteine residues that are conserved among TIMPs, and which are important for their activity and structure. In the present study, three tryptophan residues conserved among TIMPs were revealed to be important for the secretion of TIMP‑2. Replacement of conserved tryptophan residues in TIMP‑2 with alanine led to a decrease in extracellular TIMP‑2 levels and an increase in intracellular TIMP‑2 levels. Furthermore, wild‑type TIMP‑2 and TIMP‑2 mutated at unconserved tryptophan residues mainly localized in the Golgi apparatus, while TIMP‑2 proteins mutated at conserved tryptophan were mainly observed in the endoplasmic reticulum (ER). This indicated that conserved tryptophan is essential for transporting TIMP‑2 from the ER to Golgi apparatus. These observations suggested that conserved tryptophan residues among the TIMP family of proteins have critical roles for ER‑Golgi transport and subsequent secretion of TIMP‑2.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Involvement of conserved tryptophan residues for secretion of TIMP‑2

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