Lorén C E, Scully A, Grabbe C, Edeen P T, Thomas J, McKeown M, Hunter T, Palmer R H
Umeå Center for Molecular Pathogenesis, Building 6L, Umeå University, S-901 87, Sweden.
Genes Cells. 2001 Jun;6(6):531-44. doi: 10.1046/j.1365-2443.2001.00440.x.
The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described.
We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK.
In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.
哺乳动物受体蛋白酪氨酸激酶（RTK），间变性淋巴瘤激酶（ALK），最初被描述为在非霍奇金淋巴瘤中发现的t(2;5)染色体易位的产物。虽然已经研究了非霍奇金淋巴瘤中ALK激活的机制，但迄今为止，尚未描述这种孤儿胰岛素受体家族RTK在体内的作用。
我们在此描述了一种新的果蝇RTK，DAlk，我们已将其定位到第二条染色体右臂的53区带。全长DAlk cDNA编码一种200 kDa的磷蛋白，它不仅与哺乳动物ALK具有同源性，而且与孤儿RTK LTK也具有同源性。对哺乳动物和果蝇ALK的分析表明，RTK的ALK家族在其细胞外区域包含一个新鉴定的MAM结构域。与其哺乳动物对应物一样，通过原位分析，DAlk似乎在发育中的中枢神经系统中表达。然而，除了DAlk在果蝇大脑中的表达外，仔细分析还发现DAlk在发育中的内脏中胚层中还有一个额外的早期作用，其表达与激活的ERK一致。
在本文中，我们描述了一种在发育中的胚胎中胚层和中枢神经系统中表达的果蝇Alk RTK。我们的数据为果蝇中存在DAlk RTK途径提供了证据。我们表明ERK参与了该途径，并且它在体内被DAlk激活。dALK与激活的ERK的表达模式表明，DAlk符合缺失的RTK途径的标准，导致发育中的内脏中胚层中的ERK激活。
