Abstract
Phosphorylation plays a central role in regulating signal transduction across all kingdoms of life, allowing organisms to sense and respond to their environment. In mammals, the signalling research field is dominated by the functions of pSer, pThr and pTyr, due to both historical and technological factors. Mostly ignored are the labile phosphosites (LaPhs), made up of six other phosphorylatable amino acids: His, Lys, Arg, Asp, Glu and Cys. This group is characterised by an acid and/or heat-labile phosphate linkage, forming a distinct group from the highly stable phosphomonoesters of pSer, pThr and pTyr. LaPhs have distinct thermal and pH stability profiles, which may contribute to, or even dictate, their functions. Here, we review the contribution of LaPhs to mammalian signalling networks, highlighting their currently defined diverse functions.