Regulation of glycosyltransferases in ganglioside biosynthesis by phosphorylation and dephosphorylation

The biosynthesis of gangliosides is known to be under strict metabolic cont rol. One level of control is through post-translational modification of the glycosyltransferases responsible for their biosynthesis. Thus, the activit ies of several sialyltransferases have been demonstrated to be downregulate d by the action of protein kinase C (PKC) in cell-free and intact cell syst ems. This modulatory effect can be reversed at least in part by the action of membrane-bound phosphatases. In contrast, the activity of N-acetylgalact osaminyltransferase can be upregulated by the action of protein kinase A (P KA) in cultured cells. In addition, studies from several laboratories have demonstrated that phosphorylation of certain glycosyltransferases can affec t their intracellular processing and translocation. Thus, modulation of gly cosyltransferases by phosphorylation and dephosphorylation should represent an important regulatory mechanism for ganglioside biosynthesis. (C) 2001 E lsevier Science Ireland Ltd. All rights reserved.