IDENTIFICATION OF A NOVEL FORM OF THE ALPHA(3) INTEGRIN SUBUNIT - COVALENT ASSOCIATION WITH TRANSFERRIN RECEPTOR

The alpha(3) beta(1) integrin is a cell-surface receptor for laminin, entactin, collagen, fibronectin and epiligrin. On some prostatic-carci noma cell lines that express the alpha 3 beta(1) heterodimer we have i dentified a novel form of the alpha 3 subunit. Whereas the prototypic alpha 3 subunit has a molecular mass of similar to 155 kDa, we have is olated a similar to 225 kDa protein (p225) which is recognized by mono clonal antibodies to the alpha(3) subunit. Protein sequence analysis r evealed that p225 consists of two polypeptides, namely integrin alpha( 3) heavy chain (similar to 130 kDa) disulphide-bonded to a monomer of the transferrin receptor (similar to 95 kDa) instead of the typical al pha(3) light chain (similar to 25 kDa). The p225 seems to be directly associated with beta(1)subunit, since it was immunoprecipitable with a nti-(beta 1subunit) antibodies. The association of transferrin recepto r and integrin alpha(3) was apparently not the result of spurious disu lphide-bond formation occurring during the protein purification, as io doacetamide and GSH did not block the formation of the complex. The tr ansferrin receptor is normally a homodimer that is involved in the int ernalization ofiron-bound transferrin into cells and can be expressed at relatively high levels in the cell lines which we have studied. The p225 is not found on all cell types examined to date and therefore it may represent a unique complex between the integrin alpha(3) subunit and the transferrin receptor, a covalent association which may play a role in the adherence and/or proliferation of some types of tumour cel ls.