Characterization of a novel ligand for Receptor Tyrosine Kinase ErbB

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A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned.Five alternative spliced isoforms (alpha1, alpha 2 a alpha2b, beta, gamma) have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells.The rat NTAKalpha2a isoform exhibits 94% identity in its primary sequence with the human NTAKalpha isoform.In vivo, NTAK is only expressed in the brain of rat E11.5 embryos, and in the brain and thymus of adult rats.The soluble 46 kDa form binds directly to ErbB3 and B4, but not to ErbB1 or B2.NTA,K except gamma-isofrom, however, transactivates ErbB1 and B2 via heterodimerization with ErbB3 or B4.NTAK stimulates the differentiation of MDA-MB--453 cells and competitively inhibits the binding of 125I-neuregulin to these cells.In addition to these neuregulin-like properties, NTAK exhibits limited structural homology to neuregulins in the immunoglobulin (Ig)-like, EGF-like and hydrophobic domains.Thus, NTAK appears to be a new member of the EGF family displaying neuregulin properties.