HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakahara, S. Articles by Miyoshi, E. Search for Related Content PubMed PubMed Citation Articles by Nakahara, S. Articles by Miyoshi, E.

A secreted type of ß1,6 N-acetylglucosaminyltransferase V (GnT-V), a novel angiogenesis inducer, is regulated by -secretase

Susumu Nakahara^*,, Takashi Saito^*, Nami Kondo^*, Kenta Moriwaki^*, Katsuhisa Noda^*, Shinji Ihara^*, Motoko Takahashi^*, Yoshihito Ide^*, Jianguo Gu^*, Hidenori Inohara, Taiichi Katayama^,¶, Masaya Tohyama, Takeshi Kubo, Naoyuki Taniguchi^*, and Eiji Miyoshi^*,1

^* Department of Biochemistry,

Department of Otolaryngology and Sensory Organ Surgery,

Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;

Department of Disease Glycomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; and

^¶ Department of Anatomy, Hamamatsu University School of Medicine, Shizucka, Japan

¹Correspondence: Department of Biochemistry, Osaka University Graduate School of Medicine, 2–2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: miyoshi34{at}biochem.med.osaka-u.ac.jp

Glycosyltransferases are present in the Golgi apparatus in a membrane-bound form and are released from cells after cleavage by certain proteases. ß1,6-N-Acetylglucosaminyltransferase V (GnT-V), which is cleaved and secreted from the cells, is involved in the biosynthesis of ß1–6GlcNAc branching on N-glycans and has been implicated in tumor progression and metastasis. We recently reported that a secreted type of GnT-V (soluble GnT-V) itself could promote angiogenesis, which is completely different from its original function as a glycosyltransferase, and this might play a role in tumor invasion. In this study, to explore the molecular basis for this functional glycosyltransferase secretion, its cleavage site was examined and the protease(s) involved in that cleavage were identified. The NH₂-terminal protein sequence of purified soluble GnT-V (100 kDa) from GnT-V-overexpressed cells revealed that its terminus started at His³¹, located at the boundary position between the transmembrane and stem regions. This secretion was not inhibited by a single amino acid mutation at the cleavage site (Leu²⁹, Leu³⁰ to Asp, His³¹ to Ala), but specifically inhibited by addition of DFK-167, a -secretase inhibitor, suggesting that -secretase is a plausible protease for secretion processing. In addition, transfection of the gene of familial Alzheimer’s disease (FAD)-linked presenilin-1, a component of -secretase, increased the secretion rate of endogenous GnT-V; the secretion of soluble GnT-V (100 kDa) was completely inhibited in presenilin-1/2 double-deficient cells, which have no -secretase activity. Collectively, these results demonstrate that Golgi-resident GnT-V is cleaved at the transmembrane region by -secretase, and this might control tumor angiogenesis through a novel pathway.—Nakahara, S., Saito, T., Kondo, N., Moriwaki, K., Noda, K., Ihara, S., Takahashi, M., Ide, Y., Gu, J., Inohara, H., Katayama, T., Tohyama, M., Kubo, T., Taniguchi, N., Miyoshi, E. A secreted type of ß1,6 N-acetylglucosaminyltransferase V (GnT-V), a novel angiogenesis inducer, is regulated by -secretase.

Key Words: glycosylation • presenilin-1 • tumor metastasis • proteases

This article has been cited by other articles:

				D. Li, Y. Li, X. Wu, Q. Li, J. Yu, J. Gen, and X.-L. Zhang Knockdown of Mgat5 Inhibits Breast Cancer Cell Growth with Activation of CD4+ T Cells and Macrophages J. Immunol., March 1, 2008; 180(5): 3158 - 3165. [Abstract] [Full Text] [PDF]