Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari School of Medicine, Bari, Italy.
Arch Physiol Biochem. 2011 Jul;117(3):116-24. doi: 10.3109/13813455.2011.562513. Epub 2011 Apr 21.
p66Shc, a 66 kDa proto-oncogene Src collagen homologue (Shc) adaptor protein, is classically known as a signalling protein implicated in receptor tyrosine kinase signal transduction. The p66Shc isoform exerts a physiologically relevant, inhibitory signalling effect on the Erk pathway in skeletal muscle myoblasts, which is necessary for actin cytoskeleton polymerization and normal glucose transport responses. More recently, p66Shc has been also identified as a sensor of oxidative stress-induced apoptosis and as a longevity protein in mammals, actions which require Ser36 phosphorylation of the protein and consequent accumulation of intracellular reactive oxygen species. Oxidative stress plays a key role in dysfunction of several organs and tissues, and this is of interest in metabolic diseases such as type 2 diabetes. Thus changes in p66Shc expression and/or function may play an important role in the pathogenesis of type 2 diabetes and potentially serve as an effective target for its treatment.
p66Shc 是一种 66kDa 的原癌基因 Src 胶原同源物 (Shc) 衔接蛋白，经典上被认为是一种参与受体酪氨酸激酶信号转导的信号蛋白。p66Shc 同工型对骨骼肌成肌细胞中的 Erk 途径发挥生理相关的抑制性信号作用，这对于肌动蛋白细胞骨架聚合和正常葡萄糖转运反应是必需的。最近，p66Shc 也被确定为氧化应激诱导凋亡的传感器和哺乳动物中的长寿蛋白，这些作用需要蛋白质的 Ser36 磷酸化和随之而来的细胞内活性氧物质的积累。氧化应激在多个器官和组织的功能障碍中起着关键作用，这在代谢疾病如 2 型糖尿病中很重要。因此，p66Shc 的表达和/或功能的变化可能在 2 型糖尿病的发病机制中起重要作用，并可能成为其治疗的有效靶点。
