The CD98 (4F2, FRP-1) is a widely expressed cell surface protein heterodimer composed of a glycosylated heavy chain and a non-glycosylated light chain. Originally described as a T cell activation antigen, it was later shown to function in amino acid transport, cell fusion and homotypic cell aggregation. Several lines of evidence suggest its functional interaction with integrins but the biochemical basis for this interaction has been unclear.

The 80/40-kDa CD98 protein. complex was purified using an anti-CD98 heavy chain monoclonal antibody coupled to Sepharose beads. fluted proteins were subjected to preparative SDS-polyacrylamide gel electrophoresis, and protein corresponding to the 40-kDa CD98 light chain was excised. Following proteolysis with trypsin, a peptide fragment was sequenced by mass spectrometry. The nine residues obtained we:re identical to established C-terminal sequences of the human E16 and rat TAI proteins, suggesting that TA1/E16 protein is the CD98 Light chain. Consistent with this, anti-TA1/E16 antibodies specifically immunoblotted the similar to 35-40-kDa light chain present upon immunoprecipitation of the human CD98 complex. Furthermore, anti-CD98 heavy chain antibody specifically co-immunoprecipitated hemagglutinin-tagged light chain from cells transfected with hemagglutinin-tagged E16 cDNA. In conclusion, the CD98 light chain is identical to the TA1/E16 protein, based on partial amino acid sequence identity, antibody crossreactivity, genetic reconstitution evidence, similar molecular size, and comparable cell distribution.