THE CELL-ADHESION MOLECULE, GP116, IS A NEW CD44 VARIANT (EX14 V10) INVOLVED IN HYALURONIC-ACID BINDING AND ENDOTHELIAL-CELL PROLIFERATION/

In this study we have found that endothelial cells from different orig ins all contain a CD44-related transmembrane glycoprotein, named GP116 . Using a bovine aortic endothelial cell line and a standard pulse-cha se protocol, we show that GP116 is synthesized as a 52-kDa nascent pol ypeptide precursor (p52) which is processed to GP116 as follows, p52 - -> p63/65 --> p82 --> p100 --> GP116. GP116 contains approximate to 8 N- and approximate to 11 O-linked oligosaccharide chains (but lacks gl ycosaminoglycans) and interacts directly with the cytoskeletal protein , ankyrin, both in vitro (K-d approximate to 1.2 nM) and in vivo. The results of GP116 amino acid composition, reverse transcriptase polymer ase chain reaction, Southern blot, Northern blot, cloning, and sequenc e analyses indicate that endothelial cells express this new CD44 varia nt that contains an exon having significant homology with human CD44 e xon 14 (ex14/v10). GP116, designated as CD44 (ex14/v10), has been show n to be a major hyaluronic acid (HA) receptor (K-d approximate to 0.5- 0.8 nM) responsible for cell adhesion. Most importantly, we have found that the interaction between CD44(ex14/v10) and HA or a small fragmen t of HA (10-15 disaccharide units) induces a mitogenic response in end othelial cells, These findings suggest that this CD44 variant plays an important role in regulating endothelial cell proliferation.