PROTEIN-STRUCTURE OF FETAL ANTIGEN-1 (FA1) - A NOVEL CIRCULATING HUMAN EPIDERMAL-GROWTH-FACTOR-LIKE PROTEIN EXPRESSED IN NEUROENDOCRINE TUMORS AND ITS RELATION TO THE GENE-PRODUCTS OF DLK AND PG2

The present paper describes the primary structure, glycosylation and t issue localization of fetal antigen 1 (FA1) isolated from second-trime ster human amniotic fluid. FA1 is a single-chained, heterogeneous glyc oprotein of 225-262 amino acid residues. FA1 has six well conserved ep idermal-growth-factor motifs and contains up to ten O-glycosylation an d N-glycosylation sites, six of which are differentially glycosylated. Alignment to the translated sequences of Mus. musculus dlk and human dlk revealed 86% and 99% identity, respectively, to a 259-amino-acid r esidue overlap, and this high similarity extends with minor correction s to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact to the vasc ular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Lang erhans. Our findings suggest that FA1 is synthesized as a membrane anc hored protein and released into the circulation after enzymic cleavage , and that circulating FA1 represents the post-translationally modifie d gene product of human dlk which, in turn, is identical to human adre nal-specific mRNA pG2.