Skip Navigation


Journal of Biochemistry Advance Access originally published online on November 26, 2007
Journal of Biochemistry 2008 143(3):359-367; doi:10.1093/jb/mvm228
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
143/3/359    most recent
mvm228v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Kawakami, F.
Right arrow Articles by Ohtsuki, K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawakami, F.
Right arrow Articles by Ohtsuki, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Japanese Biochemical Society.

Biochemical Characterization of Phospholipids, Sulfatide and Heparin as Potent Stimulators for Autophosphorylation of GSK-3β and the GSK-3β-Mediated Phosphorylation of Myelin Basic Protein In vitro

Fumitaka Kawakami1, Akira Yamaguchi1, Kanzo Suzuki1, Takayuki Yamamoto2 and Kenzo Ohtsuki1,*

1Laboratory of Genetical Biochemistry and Signal Biology, Graduate School of Medical Sciences; and 2Biological Laboratory, Center for Natural Sciences, Kitasato University, Sagamihara 228-8555, Japan

*To whom correspondence should be addressed. Tel/Fax: +81-42-778-8863, E-mail: ken{at}kitasato-u.ac.jp

Received October 21, 2007; Accepted November 13, 2007


  Abstract

The stimulatory effects of SH (sulfatide and heparin) and two phospholipids (PI and PS) on autophosphorylation of GSK-3β and the GSK-3β-mediated phosphorylation of myelin basic protein (MBP) and two synthetic MBP peptides (M86 and M156) were comparatively examined in vitro. It was found that (i) both PI and SH highly stimulated the GSK-3β-mediated phosphorylation of MBP, but not glycogen synthase, and two MBP peptides through their direct binding to these substrates and (ii) both PI and heparin, as compared with sulfatide, highly stimulated autophosphorylation of GSK-3β. The Km value of MBP for GSK-3β was highly reduced and the Vmax value was significantly increased in the presence of these acidic modulators, which augmented further phosphorylation of MBP by the kinase. Under our experimental condition, similar stimulatory effects of PI and heparin were observed with the GSK-3β-mediated phosphorylation of tau protein (TP) in vitro. These results presented here suggest that these two phospholipids and SH may function as effective stimulators for autophosphorylation of GSK-3β and for the GSK-3β-mediated high phosphorylation of SH-binding proteins, including MBP and TP, in the highly accumulated levels of these acidic and sulfated modulators in the brain.

Key Words: glycogen synthase, glycogen synthase kinase 3, heparin, myelin basic protein, phospholipid, sulfatide, tau-kinase, tau protein

Abbreviations: AD, Alzheimer's disease; A-kinase, cAMP-dependent protein kinase; CDK-5, cycline-dependent protein kinase-5; CH-3S, cholesterol-3-sulfate; CK1, casein kinase 1; C-kinase, Ca2+/phospholipid-dependent protein kinase; DTT, dithiothreitol; GS, glycogen synthase; GSK-3β, glycogen synthase kinase-3β; MBP, myelin basic protein; PI, phosphatidylinositol; PS, phosphatidylserine; QCM, quarts crystal microbalance; SH, sulfatide and heparin; TP, tau protein


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.