摘要：

TGF-α and EGF are structurally related factors that bind to and induce tyrosine autophosphorylation of a common receptor. Proteolytic cleavage of the transmembrane TGF-α precursor's external domain releases several TGF-α species. However, membrane-bound TGF-α forms remain on the surface of TGF-α-expressing cell lines. To evaluate the biological activity of these forms, we modified two cleavage sites in the TGF-α precursor coding sequence, making processing into the 50 amino acid TGF-α impossible. Overexpression of this cDNA in a receptor-negative cell line, partial purification, and N-terminal sequence analysis indicate the existence of two transmembrane TGF-α forms. These solubilized precursors induce tyrosine autophosphorylation of the EGF/TGF-α receptor in intact receptor-overexpressing cells, and anchorage-independent growth of NRK fibroblasts. Cell-cell contact between TGF-α precursor-overexpressing cells and cells expressing high numbers of receptors also resulted in receptor activation. These findings suggest a role for transmembrane TGF-α forms in intercellular interactions in proliferating tissues.

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