Sorci Guglielmo, Riuzzi Francesca, Arcuri Cataldo, Tubaro Claudia, Bianchi Roberta, Giambanco Ileana, Donato Rosario
Guglielmo Sorci, Francesca Riuzzi, Cataldo Arcuri, Claudia Tubaro, Roberta Bianchi, Ileana Giambanco, Rosario Donato, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
World J Biol Chem. 2013 Feb 26;4(1):1-12. doi: 10.4331/wjbc.v4.i1.1.
The Ca(2+)-binding protein of the EF-hand type, S100B, exerts both intracellular and extracellular regulatory activities. As an intracellular regulator, S100B is involved in the regulation of energy metabolism, transcription, protein phosphorylation, cell proliferation, survival, differentiation and motility, and Ca(2+) homeostasis, by interacting with a wide array of proteins (i.e., enzymes, enzyme substrates, cytoskeletal subunits, scaffold/adaptor proteins, transcription factors, ubiquitin E3 ligases, ion channels) in a restricted number of cell types. As an extracellular signal, S100B engages the pattern recognition receptor, receptor for advanced glycation end-products (RAGE), on immune cells as well as on neuronal, astrocytic and microglial cells, vascular smooth muscle cells, skeletal myoblasts and cardiomyocytes. However, RAGE may not be the sole receptor activated by S100B, the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types. Moreover, extracellular effects of S100B vary depending on its local concentration. Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury, which is up to a few nM levels, S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis. The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development, repair and regeneration.
EF 手型钙结合蛋白 S100B 具有细胞内和细胞外调节活性。作为细胞内调节因子，S100B 通过与多种蛋白质（如酶、酶底物、细胞骨架亚基、支架/衔接蛋白、转录因子、泛素 E3 连接酶、离子通道）在有限数量的细胞类型中相互作用，参与能量代谢、转录、蛋白质磷酸化、细胞增殖、存活、分化和运动以及钙稳态的调节。作为一种细胞外信号，S100B 可与免疫细胞以及神经元、星形胶质细胞、小胶质细胞、血管平滑肌细胞、骨骼肌成肌细胞和心肌细胞上的模式识别受体——晚期糖基化终产物受体（RAGE）结合。然而，RAGE 可能不是 S100B 激活的唯一受体，该蛋白能够在特定细胞类型中通过与结合 FGFR1 的 bFGF 相互作用来增强 bFGF - FGFR1 信号传导。此外，S100B 的细胞外效应因其局部浓度而异。越来越多的证据表明，在正常生理条件下细胞外液以及急性组织损伤局部所发现的浓度（高达几纳摩尔水平）下，S100B 在中枢和外周神经系统以及骨骼肌组织中发挥营养作用，从而参与组织稳态。本述评总结了表明细胞内和细胞外 S100B 参与组织发育、修复和再生的研究结果。
