[Two forms of precursors of a heparin-binding EGF-like growth factor-diphtheria toxin receptor].

A new mRNA coding for the heparin-binding EGF-like growth factor (HB-EGF) was found in Vero cells. The corresponding cDNA had C-156 in place of T, which resulted in a loss of the NheI site and a substitution of Leu-33 with Pro in the HB-EGF precursor. The known and new forms of the precursor were accordingly termed L and P. A possible conformational change in the corresponding propeptide region were assumed to affect processing of soluble secreted HB-EGF. The L and P mRNAs are differently expressed in various cell lines and have the identical 5'-untranslated sequences. Possibly, they are transcribed from one promoter and then alternatively spliced. Stimulation of resting Vero cells with tetraphorbol ester (TPA) substantially increased production of the L form, decreased production of the P form, and did not affect expression of the total HB-EGF mRNA. This was associated with an increase in binding of the diphtheria toxin, suggesting that the L HB-EGF precursor acts as its receptor.