Characterization of a novel ligand for Receptor Tyrosine Kinase ErbB

表皮生长因子（EGF）家族的一个新成员--神经和胸腺来源的ErbB激酶激活剂（NTAK）已被纯化和克隆。（α 1，α 2 a α 2b，β，γ）已在大鼠肾上腺嗜铬细胞瘤细胞系中检测到，大鼠NTAK α 2a同种型在其一级序列中与人NTAK α同种型具有94%的同一性。可溶性46 kDa型与ErbB_3和B_4直接结合，但不与ErbB_1或B_2结合。NTAK通过与ErbB 3或B4的异源二聚体化反式激活ErbB 1和B2。NTAK刺激MDA-MB-453细胞的分化，并竞争性抑制125 I-除了这些神经调节蛋白样的性质，NTAK在免疫球蛋白（IG）样、EGF样和疏水结构域中显示出与神经调节蛋白有限的结构同源性，因此，NTAK似乎是显示神经调节蛋白性质的EGF家族的新成员。

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.