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SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function
Journal article   Peer reviewed

SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function

Takako Yoshida-Moriguchi, Tobias Willer, Mary E Anderson, David Venzke, Tamieka Whyte, Francesco Muntoni, Hane Lee, Stanley F Nelson, Liping Yu and Kevin P Campbell
Science (American Association for the Advancement of Science), Vol.341(6148), pp.896-899
08/23/2013
DOI: 10.1126/science.1239951
PMCID: PMC3848040
PMID: 23929950

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Abstract

Phosphorylated O-mannosyl trisaccharide [N-acetylgalactosamine-β3-N-acetylglucosamine-β4-(phosphate-6-)mannose] is required for dystroglycan to bind laminin-G domain-containing extracellular proteins with high affinity in muscle and brain. However, the enzymes that produce this structure have not been fully elucidated. We found that glycosyltransferase-like domain-containing 2 (GTDC2) is a protein O-linked mannose β 1,4-N-acetylglucosaminyltransferase whose product could be extended by β 1,3-N-acetylgalactosaminyltransferase2 (B3GALNT2) to form the O-mannosyl trisaccharide. Furthermore, we identified SGK196 as an atypical kinase that phosphorylated the 6-position of O-mannose, specifically after the mannose had been modified by both GTDC2 and B3GALNT2. These findings suggest how mutations in GTDC2, B3GALNT2, and SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy.
 Protein Kinases - metabolism Phosphorylation Protein Kinases - genetics Humans Dystroglycans - metabolism N-Acetylglucosaminyltransferases - genetics Glycosylation N-Acetylglucosaminyltransferases - metabolism Glycosyltransferases - metabolism N-Acetylgalactosaminyltransferases - genetics HEK293 Cells Protein Processing, Post-Translational Glycosyltransferases - genetics N-Acetylgalactosaminyltransferases - metabolism Trisaccharides - metabolism

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