| Research Abstract |
To understand the pathway of signal transduction related to CD98-mediated malignant transformation, the following investigations were planned ; 1) Production of monoclonal antibodies against CD98lc and CD98-associated molecules, 2) Molecular cloning of cDNAs for CD98-associated molecules and 3) Establishment and analysis of full-length, truncated or point-mutated CD98hc-transfected cell clones.
1) We produced monoclonal antibodies recognizing a novel CD98lc isoform, and demonstrated that expression of CD98lc is upregulated by lymphocyte activation and cellular transformation, as in the case with the expression of CD98hc. We also produced monoclonal antibodies against humal renal cancer, and identified tropomyosin isoforms as CD98-associated molecules. Interestingly, colocalization of CD98 and tropomyosin was characteristically observed in the cell-cell adhesion boundary.
2) We cloned cDNAs for full-length and truncated glutamate transporter (EAAC-1), which has partial amino-acid homology with CD98lc.
3) We established and analysed full-length (wild-type), truncated and point-mutated CD98hc-transfected cell clones, and demonstrated the relationship between the overexpression of CD98hc and malignant transformation, requirement of the binding between inherent CD98lc and introduced CD98hc, and enhanced tumorigenicity caused by truncation of the extracellular domain of CD98hc.
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