Cell-cell Adhesion and CD98 as an Adhesion Regulator

CD98 is expressed on both haematopoietic and non-haematopoietic cells and has been implicated in a variety of different functional roles such as amino acid transport, oncogenic transformation and cell adhesion and fusion. L ittle is known about molecular mechanism of CD98 function, including interaction with other molecules and signalling pathways induced by CD08 activation. The first part of this study examined the functional interactions between CD98 and other adhesion molecules such as CD29 and CD147 on the surface of the promonocyte line U937, using a quantitative assay of cell aggregation and blocking monoclonal antibodies to adhesion molecules. Two antibodies to CD147, an immunoglobulin superfamily member whose function has remained unclear, were potent inhibitors of the aggregation induced via the ligation of both CD98 and CD29. CD98 blocking mAbs also diminished CD29-induced homotypic aggregation. The results suggest that CD98, CD29 and CD147 are functionally associated within a multi-molecular unit which regulates cell-cell adhesion. To dissect signalling pathways induced by CD98 activation, CD98-mediated U937 homotypic aggregation was further carefully evaluated with pharmacological and biochemical approaches. CD08 ligation induced a selective membrane translocation of the novel PKCs isoform, as an essential step in mediating IB37 homotypic aggregation. CD98-induced PKCs activation continuously mediated activation of MAPK, Erkl/2 and p38, as well as tyrosine phosphorylation. Collectively, CD98 activation may be selectively linked to PKCs activation. These results provide new information on how CD98 regulates cellular function via induction of signalling and association with other surface molecules.