Balemans Wendy, Van Hul Wim
Department of Medical Genetics, University of Antwerp and University Hospital, Antwerp 2610, Belgium.
Dev Biol. 2002 Oct 15;250(2):231-50.
The transforming growth factor-beta (TGF-beta) superfamily contains a variety of growth factors which all share common sequence elements and structural motifs. These proteins are known to exert a wide spectrum of biological responses on a large variety of cell types in both vertebrates and invertebrates. Many of them have important functions during embryonic development in pattern formation and tissue specification, and in adult tissues, they are involved in processes such as wound healing, bone repair, and bone remodeling. The family is divided into two general branches: the BMP/GDF and the TGF-beta/Activin/Nodal branches, whose members have diverse, often complementary effects. It is obvious that an orchestered regulation of different actions of these proteins is necessary for proper functioning. The TGF-beta family members act by binding extracellularly to a complex of serine/threonine kinase receptors, which consequently activate Smad molecules by phosphorylation. These Smads translocate to the nucleus, where they modulate transcription of specific genes. Three levels by which this signaling pathway is regulated could be distinguished. First, a control mechanism exists in the intracellular space, where inhibitory Smads and Smurfs prevent further signaling and activation of target genes. Second, at the membrane site, the pseudoreceptor BAMBI/Nma is able to inhibit further signaling within the cells. Finally, a range of extracellular mediators are identified which modulate the functioning of members of the TGF-beta superfamily. Here, we review the insights in the extracellular regulation of members of the BMP subfamily of secreted growth factors with a major emphasis on vertebrate BMP modulation.
转化生长因子-β(TGF-β)超家族包含多种生长因子,它们都具有共同的序列元件和结构基序。已知这些蛋白质对脊椎动物和无脊椎动物的多种细胞类型都会产生广泛的生物学反应。其中许多在胚胎发育过程中的模式形成和组织特化中具有重要功能,在成体组织中,它们参与伤口愈合、骨修复和骨重塑等过程。该家族分为两个主要分支:BMP/GDF分支和TGF-β/激活素/节点分支,其成员具有多样且往往互补的作用。显然,对这些蛋白质的不同作用进行协调调节对于其正常功能是必要的。TGF-β家族成员通过在细胞外与丝氨酸/苏氨酸激酶受体复合物结合来发挥作用,进而通过磷酸化激活Smad分子。这些Smad分子转移到细胞核,在那里调节特定基因的转录。可以区分该信号通路被调节的三个水平。首先,在细胞内空间存在一种控制机制,其中抑制性Smad和Smurf可阻止进一步的信号传导和靶基因的激活。其次,在膜位点,假受体BAMBI/Nma能够抑制细胞内的进一步信号传导。最后,已鉴定出一系列细胞外介质,它们可调节TGF-β超家族成员的功能。在此,我们综述分泌型生长因子BMP亚家族成员细胞外调节方面的见解,重点是脊椎动物BMP的调节。
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