IDENTIFICATION OF IHABP, A 95KDA INTRACELLULAR HYALURONATE BINDING-PROTEIN

The extracellular matrix component hyaluronan is believed to play impo rtant roles in various processes of organogenesis, cell migration and cancer. Recognition of and binding to hyaluronan is mediated by cell s urface receptors, Three of them, CD44, ICAM-1 and RHAMM (receptor for hyaluronic acid mediated motility), have been identified. A cDNA clone designated RHAMM turned out to possess transforming capacity. Based o n this published sequence, we isolated the complete cDNA of the murine gene. The cDNA comprises an open reading frame of 2.3 kb and encodes a 95 kDa protein. The protein carries a hyaluronan binding motif which binds to hyaluronan in vitro but not to heparin or chondroitin sulpha te. It is ubiquitously expressed in normal cells and in all tumour cel l lines irrespective of their metastatic properties. One tumour cell l ine, the metastatic Lewis lung carcinoma, expresses a larger 105 kDa v ariant form of the protein due to a genomic rearrangement. Antibodies raised against the 95 kDa protein were used for subcellular localizati on studies. The hyaluronan binding protein is not detectable at the ce ll surface but is rather localized exclusively intracellularly, Clearl y, the sequence we have identified encodes a protein with properties s ubstantially different to the RHAMM protein. We tentatively name the p rotein intracellular hyaluronic acid binding protein, IHABP.