Calderwood Stuart K, Mambula Salamatu S, Gray Philip J, Theriault Jimmy R
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
FEBS Lett. 2007 Jul 31;581(19):3689-94. doi: 10.1016/j.febslet.2007.04.044. Epub 2007 Apr 25.
Extracellular stress proteins including heat shock proteins (Hsp) and glucose regulated proteins (Grp) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological "danger signals". Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis. After release into the extracellular fluid, Hsp or Grp may then bind to the surfaces of adjacent cells and initiate signal transduction cascades as well as the transport of cargo molecules such as antigenic peptides. In addition Hsp60 and hsp70 are able to enter the bloodstream and may possess the ability to act at distant sites in the body. Many of the effects of extracellular stress proteins are mediated through cell surface receptors. Such receptors include Toll Like Receptors 2 and 4, CD40, CD91, CCR5 and members of the scavenger receptor family such as LOX-1 and SREC-1. The possession of a wide range of receptors for the Hsp and Grp family permits binding to a diverse range of cells and the performance of complex multicellular functions particularly in immune cells and neurones.
包括热休克蛋白（Hsp）和葡萄糖调节蛋白（Grp）在内的细胞外应激蛋白正逐渐成为细胞间信号传导和运输的重要介质。此类蛋白从细胞中的释放是由物理创伤、行为应激以及接触免疫“危险信号”触发的。应激蛋白的释放既通过生理分泌机制发生，也在细胞坏死导致的细胞死亡过程中发生。释放到细胞外液后，Hsp或Grp可能会与相邻细胞的表面结合，并启动信号转导级联反应以及诸如抗原肽等货物分子的运输。此外，Hsp60和hsp70能够进入血液，并可能具有在身体远处部位发挥作用的能力。细胞外应激蛋白的许多作用是通过细胞表面受体介导的。此类受体包括Toll样受体2和4、CD40、CD91、CCR5以及清道夫受体家族的成员，如LOX-1和SREC-1。Hsp和Grp家族拥有广泛的受体，这使得它们能够与多种细胞结合，并执行复杂的多细胞功能，尤其是在免疫细胞和神经元中。
