Skip Navigation



Glycobiology Advance Access published online on January 23, 2006
Glycobiology, doi:10.1093/glycob/cwj078
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
16/5/415    most recent
cwj078v1
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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lazarus, B. D
Right arrow Articles by Hanover, J. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lazarus, B. D
Right arrow Articles by Hanover, J. A
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2006
Received November 7, 2005
Revised January 12, 2006
Accepted January 13, 2006

Article

Recombinant O-GlcNAc Transferase Isoforms: Identification of O-GlcNAcase, YES tyrosine kinase and Tau as Isoform-specific substrates

Brooke D Lazarus 1, Dona C Love 1, and John A Hanover 1 *

1 Laboratory of Cell Biology and Biochemistry, NIDDK, National Institutes of Health

* To whom correspondence should be addressed.
John A Hanover, E-mail: jah{at}helix.nih.gov


  Abstract

O-linked N-Acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked GlcNAc to serine/threonine residues of a variety of substrate proteins, including nuclear pore proteins, transcription factors and proteins implicated in diabetes and neurodegenerative disorders. We have identified two nucleocytoplasmic isoforms of OGT (ncOGT and sOGT) and one isoform that localizes to the mitochondria (mOGT). These three isoforms contain identical catalytic regions but differ in the number of TPR motifs found at the N-terminus of each enzyme. We expressed each of these OGT isoforms in a soluble form in E. coli and have used them to identify novel targets including the Src-family tyrosine kinase yes and O-GlcNAcase. We demonstrate that some substrate proteins, such as Nup62 and CKII are glycosylated by both ncOGT and mOGT, while others such as O-GlcNAcase and tau are specifically modified by ncOGT. The yes kinase was specifically modified by mOGT. The short isoform of OGT (sOGT) did not glycosylate any of the substrates tested although it retains a potentially active catalytic domain. Our findings demonstrate the potential utility of recombinant OGT in identifying new targets and illustrate the necessity to examine all active isoforms of the enzyme. The identification of a tyrosine kinase and O-GlcNAcase as OGT targets suggests the potential for OGT participation in numerous signal transduction cascades.

Keywords: Glycosylation/Isoform/O-GlcNAc transferase/O-GlcNAcase/tau.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
Y. Hu, J. Suarez, E. Fricovsky, H. Wang, B. T. Scott, S. A. Trauger, W. Han, Y. Hu, M. O. Oyeleye, and W. H. Dillmann
Increased Enzymatic O-GlcNAcylation of Mitochondrial Proteins Impairs Mitochondrial Function in Cardiac Myocytes Exposed to High Glucose
J. Biol. Chem., January 2, 2009; 284(1): 547 - 555.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. Whelan, M. D. Lane, and G. W. Hart
Regulation of the O-Linked {beta}-N-Acetylglucosamine Transferase by Insulin Signaling
J. Biol. Chem., August 1, 2008; 283(31): 21411 - 21417.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Marz, J. Stetefeld, K. Bendfeldt, C. Nitsch, J. Reinstein, R. L. Shoeman, B. Dimitriades-Schmutz, M. Schwager, D. Leiser, S. Ozcan, et al.
Ataxin-10 Interacts with O-Linked beta-N-Acetylglucosamine Transferase in the Brain
J. Biol. Chem., July 21, 2006; 281(29): 20263 - 20270.
[Abstract] [Full Text] [PDF]


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.