Regulation of cellular phosphorylation of hyaluronan binding protein and its role in the formation of second messenger.

The presence of the 34-kDa hyaluronan binding protein, a new member of the 'hyaladherins' family, was demonstrated in a wide variety of cell lines by immunoblot analysis. This protein was observed to be highly phosphorylated in transformed fibroblasts compared to normal fibroblasts. Phosphorylation was enhanced in the presence of its ligand i.e., hyaluronan, but not in the presence of other glycosaminoglycans. The phosphorylated form of this hyaluronan binding protein was shown to be present on the cell surface and could be detected in serum-free medium. The regulation of the cellular and cell surface phosphorylation of HA-binding protein by HA, PMA and calyculin-A was demonstrated in different cell lines. Hyaluronan enhanced the phosphorylation of PLC-gamma in association with increased formation of inositol 1,4,5-triphosphate, both of which were specifically blocked by pretreatment of the cells with purified anti-hyaluronan binding protein antibodies. The data presented here indicate a role for the 34-kDa hyaluronan binding protein in cellular signal transduction.