The Sulfogalactose Moiety of Sulfoglycosphingolipids Serves as a Mimic of Tyrosine Phosphate in Many Recognition Processes: PREDICTION AND DEMONSTRATION OF Src HOMOLOGY 2 DOMAIN/SULFOGALACTOSE BINDING

阅读量：

作者：

C Lingwood，M Mylvaganam，F Minhas，B Binnington，DR Branch，R Pomes

展开

摘要：

Multiple ligand co-recognition of 3'-sulfogalactosylceramide (SGC) and sulfotyrosine initiated the comparison of SGC and sulfotyrosine and, subsequently, phosphotyrosine (pY) binding. SGC is a receptor for ligands involved in cell adhesion/microbial pathology. pY forms a Src homology domain 2 recognition motif in intracellular signaling. Using hsp70, anti-SGC, and anti-pY antibodies, ligand binding is retained following phosphate/sulfate and tyrosine/galactose substitution in SGC and sulfate/phosphate exchange in pY. Remarkable lipid-dependent binding to phosphatidylethano-lamine-conjugated sulfotyrosine suggests "microenvironmental" modulation of sulfotyrosine-containing receptors, similar to glycosphingolipids. Based on an aryl substrate-bound co-crystal of arylsulfatase A, a sulfogalactose and phosphotyrosine esterase, modeling provides a solvation basis for co-recognition. c-Src/Src homology domain 2:SGC/phosphogalactosylceramide binding confirms our hypothesis, heralding a carbohydrate-based approach to regulation of phosphotyrosinemediated recognition.

展开

关键词：

Sulfogalactose Sulfoglycosphingolipids Tyrosine Phosphate Recognition Processes

DOI：

10.1074/jbc.m413724200

被引量：

年份：

2005