Structure and function of a novel ErbB ligand, NTAK

A novel member of the epidermal growth factor (EGF) family, the neural and thymus-derived activator for ErbB kinase (NTAK) has been cloned from the cDNA library of a rat pheochromocytoma cell line, PC12 cells and human neuroblastoma cell line, SK-N-SH cells. Four alternative spliced isoforms from rat cDNA have been detected by the methods of RT-PCR. The rat NTAKα2a isoform exhibits 94% identity in its sequence with the human NTAKα isoform. Three characteristic Ig-like, EGF-like and hydrophobic domains have been identified in rat and human NTAK molecules. Recombinant NTAK, the soluble 46 kDa form, binds directly to ErbB3 and ErbB4, but not ErbB1 and B2. NTAK, however, transactivates with heterodimer such as ErbB1/B3, B1/B4, B2/B3, B2/B4 and B3/B4. NTAK stimulates the differentiation of MDA-MB-453 cells, derived from blast carcinoma. NTAK competitively inhibits the binding of [¹²⁵I] NRG-1 to these cells. Thus, NTAK is a new member of the EGF family displaying NRG-1 properties.