Visualization of the molecular switch, c-Src, in live cells for understanding its role in signaling and cancer

摘要

Src-family kinases (SFKs) are membrane-associated nonreceptor protein tyrosine kinases that play pivotal roles in several signalling pathways. c-Src is the prototypic SFK and its activity is upregulated in a wide variety of human cancers. While the structural basis of SFK catalytic regulation is well understood, the temporal and spatial features of SFK regulation in cells are unclear. The activity of all SFKs depends on whether their conformation is "open" or "closed". In the open active conformation, the protein has an extended configuration; while in the inactive closed conformation the protein is more globular and compact. Under basal conditions in cells, c-Src is predominantly in the closed inactive state, being opened and switched on only at specific times. Dysfunctional c-Src regulation leading to high c-Src activity can result in uncontrolled cellular proliferation and cancer. However, the contribution c-Src expression or enzymatic activation in inducing and promoting cancer is still not well understood. This is partly because of a lack of approaches that enable the specific activity of c-Src to be monitored in live cells.