Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Int J Biochem Cell Biol. 2012 Mar;44(3):469-74. doi: 10.1016/j.biocel.2011.12.013. Epub 2011 Dec 31.
Ligands of the Transforming Growth Factor β superfamily like Transforming Growth Factor β and Bone Morphogenetic Proteins govern developmental processes and regulate adult homeostasis by controlling cellular proliferation, survival, differentiation and migration. Aberrant signalling activity is associated with human disorders such as cancer, cardiovascular, musculoskeletal, or fibrotic disease. Upon binding to specific sets of cognate cell surface receptors, family members induce highly similar pathways which include canonical SMAD dependent signalling as well as pathways without direct involvement of SMAD proteins, which activate signalling molecules like mitogen-activated protein kinases or small GTPases. The diverse ligand functionalities are achieved through regulation and modulation of the pathways at all levels, resulting in a highly quantitative and context sensitive signal integration reflecting the cellular state and background. Strategies to target Transforming Growth Factor β or Bone Morphogenetic Protein pathways have been developed on the basis of our current understanding and have proven a highly beneficial potential.
转化生长因子 β 超家族的配体，如转化生长因子 β 和骨形态发生蛋白，通过控制细胞增殖、存活、分化和迁移来调节发育过程和维持成人内稳态。异常的信号转导活性与人类疾病有关，如癌症、心血管、肌肉骨骼或纤维性疾病。家族成员与特定的细胞表面受体结合后，会诱导高度相似的途径，包括经典的 SMAD 依赖性信号转导以及不直接涉及 SMAD 蛋白的途径，这些途径会激活丝裂原激活蛋白激酶或小 GTP 酶等信号分子。配体的多种功能是通过在各个层面上调节和修饰途径来实现的，从而产生高度定量和上下文敏感的信号整合，反映细胞状态和背景。基于我们目前的理解，已经开发出针对转化生长因子 β 或骨形态发生蛋白途径的靶向策略，并且已经证明具有高度有益的潜力。
