Glycogenin-2 (GN-2) is a second self-glucosylating protein involved in the initiation phase of glycogen biosynthesis in mammals (Mu, J., Skurat, A. V., and Roach, P. J. (1997) J. Biol. Chem. 272, 27589-27597). In human liver extracts, most of the GN-2 was only detectable after treatment with a-amylase. Similarly, if the high Mr glycogen fraction was purified by precipitation of protein with trichloroactic acid followed by methanol precipitation, GN-2 could be released by a-amylase treatment. Liver extracts also contained glycogenin-1 (GN-1). GN-2 has significant sequence similarity to GN-1 and a Tyr residue is conserved in correspondence to Tyr-194, the site of glucose attachment in GN-1. Mutation of this residue, Tyr-228 in GN-2ct, to Phe eliminated the ability to self-glucosylate. Stable overexpression of GN-2a in Rat-1 fibroblast cells resulted in a 4-5 fold increase in the accumulation of glycogen present in the low speed pellet. Glycogen in the low speed supernatant was little changed. Total glycogen synthase activity increased in both the low speed supernatant and the pellet. Expression of the GN-2 Y228F mutant protein also caused elevated glycogen synthase activity and, to a lesser extent than wild type GN-2, an increase in glycogen accumulation. Judged by in vitro binding assays and co-immunoprecipitation studies, GN-2 was able to associate with GN-1 and the presence of GN-1 enhanced the selfglucosylation of GN-2. Whether this interaction between two glycogenin proteins is physiologically important is unknown but both isoforms are present in some cell types.
|Original language||English (US)|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Molecular Biology