O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits.
A hallmark of signal transduction is the dynamic and inducible post-translational modification of proteins. In addition to the well characterized phosphorylation of proteins, other modifications have been shown to be regulatory, including O-linked beta-N-acetylglucosamine (O-GlcNAc). O-GlcNAc modifies serine and threonine residues on a myriad of nuclear and cytosolic proteins, and for several proteins there appears to be a reciprocal relationship between phosphorylation and O-GlcNAc modification. Here we report further evidence of this yin-yang relationship by demonstrating that O-GlcNAc transferase, the enzyme that adds O-GlcNAc to proteins, exists in stable and active complexes with the serine/threonine phosphatases PP1beta and PP1gamma, enzymes that remove phosphate from proteins. The existence of this complex highlights the importance of understanding the dynamic relationship between O-GlcNAc and phosphate in modulating protein function in many cellular processes and disease states such as Alzheimer's disease and type II diabetes.
Wells
Lance
L
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. lwells@ccrc.uga.edu
Kreppel
Lisa K
LK
Comer
Frank I
FI
Wadzinski
Brian E
BE
Hart
Gerald W
GW
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000378:metabolism; D002845:Chromatography; D002850:Chromatography, Gel; D002853:Chromatography, Liquid; D003600:Cytosol / Q000378:metabolism; D013058:Mass Spectrometry; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D054645:Protein Phosphatase 1; D017434:Protein Structure, Tertiary; D051381:Rats; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry
D020033:Protein Isoforms; D013912:Threonine; D012694:Serine; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D010744:Phosphoric Monoester Hydrolases