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 origins all contain a CD44-related transmembrane glycoprotein, named GP116. Using a bovine aortic endothelial cell line and a standard pulse-chase protocol, we show that GP116 is synthesized as a 52-kDa nascent polypeptide precursor (p52) which is processed to GP116 as follows, p52 --> p63/65 --> p82 --> p100 --> GP116. GP116 contains approximately 8 N- and approximately 11 O-linked oligosaccharide chains (but lacks glycosaminoglycans) and interacts directly with the cytoskeletal protein, ankyrin, both in vitro (Kd approximately 1.2 nM) and in vivo. The results of GP116 amino acid composition, reverse transcriptase-polymerase chain reaction, Southern blot, Northern blot, cloning, and sequence analyses indicate that endothelial cells express this new CD44 variant that contains an exon having significant homology with human CD44 exon 14 (ex14/v10). GP116, designated as CD44 (ex14/v10), has been shown to be a major hyaluronic acid (HA) receptor (Kd approximately 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 fragment of HA (10-15 disaccharide units) induces a mitogenic response in endothelial cells. These findings suggest that this CD44 variant plays an important role in regulating endothelial cell proliferation.
Lokeshwar
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Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Iida
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Bourguignon
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002455:Cell Division; D004730:Endothelium, Vascular / Q000166:cytology*; D005091:Exons; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D006820:Hyaluronic Acid