p66Shc, a multifaceted protein linking Erk signalling, glucose metabolism, and oxidative stress

Abstract

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.

Keywords::

• Erk
• glucose transport
• IGF-I signalling
• oxidative stress
• Shc

Acknowledgements

This work was supported by grants from the Ministero dell’Istruzione, Università e Ricerca (MIUR, Italy) and the University of Bari, Italy to F. Giorgino, and the COST BM0602 Programme from the European Science Foundation.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.