骨形态发生蛋白的信号转导

Signal transduction by bone morphogenetic proteins.

作者信息

Kawabata M, Imamura T, Miyazono K

机构信息

Department of Biochemistry, The Cancer Institute, Tokyo, Japan.

出版信息

Cytokine Growth Factor Rev. 1998 Mar;9(1):49-61. doi: 10.1016/s1359-6101(97)00036-1.

DOI:10.1016/s1359-6101(97)00036-1

PMID:9720756

Abstract

Bone morphogenetic proteins (BMPs) are multifunctional cytokines, which are members of the transforming growth factor-beta (TGF-beta) superfamily. Activities of BMPs are extracellularly regulated by BMP-binding proteins, Noggin and Chordin. BMPs bind to two different types of serine-threonine kinase receptors, type I and type II. Two BMP type I receptors and a BMP type II receptor have been identified in mammals. Intracellular signals are transduced by Smad proteins. Smad1, Smad5 and probably MADH6, are activated by BMP receptors, form heteromeric complexes with Smad4, and translocate into the nucleus where they may activate transcription of various genes. Smad6 and Smad7 are inhibitory Smads, and may act as autocrine switch-off signals. In Drosophila melanogaster, Decapentaplegic (Dpp) is a homologue of mammalian BMPs. In this review, mechanism of action of Dpp will be discussed in comparison with that of BMPs.

摘要

骨形态发生蛋白（BMPs）是多功能细胞因子，属于转化生长因子-β（TGF-β）超家族成员。BMPs的活性在细胞外由BMP结合蛋白Noggin和Chordin调节。BMPs与两种不同类型的丝氨酸-苏氨酸激酶受体，即I型和II型受体结合。在哺乳动物中已鉴定出两种BMP I型受体和一种BMP II型受体。细胞内信号由Smad蛋白转导。Smad1、Smad5以及可能的MADH6被BMP受体激活，与Smad4形成异源复合物，并转运至细胞核，在那里它们可能激活各种基因的转录。Smad6和Smad7是抑制性Smads，可能作为自分泌关闭信号。在果蝇中，Decapentaplegic（Dpp）是哺乳动物BMPs的同源物。在本综述中，将对Dpp与BMPs的作用机制进行比较讨论。