A prismatic view of protein phosphorylation in health and disease

Citation: Via A and Zanzoni A (2015) A prismatic view of protein phosphorylation in health and disease. The paramount relevance of protein phosphorylation in health and disease motivated us to gather several contributions from experts working in this area in order to portray the recent developments in the field. Our effort and the effort of 54 authors with their 12 contributions gave rise to this Research Topic, which represents a valuable forum where phosphorylation is discussed from different angles, including bioinformatics approaches and experimental methods that are currently used to decipher the complex mechanisms underlying this bewitching post-translational modification (PTM). The articles collected in this Research Topic illustrate very diverse aspects of phosphorylation, such as its biological effects and induced structural changes, the role of kinases and phosphatases as therapeutic targets, the use of phosphorylation profiles as biomarkers, how phosphorylation dys-regulation may cause disease, and more. Nishi et al. (2014), in their extensive review of the representative studies on the biological effects of phosphorylation, show that a general mechanism of regulation by phosphorylation does not exist. Indeed, phosphorylation may serve as recognition/binding site or trigger allosteric effects inducing local structural changes, which may propagate into larger structure rearrangements. Some nice examples of the biological consequences of protein phosphorylation in physiological and disease states are described in two articles of this Research Topic. The Hsp27 protein (coded by the HSPB1 gene) is a chaperone that is aberrantly expressed in many types of tumors and represents a promising drug target (Acunzo et al., 2014). Phosphory-lation of serine residues affects the oligomerization state of Hsp27, favoring the recruitment of different client proteins involved in distinct cellular functions (Katsogiannou et al., 2014a). Kat-sogiannou et al. (2014b) suggest that better understanding Hsp27 phosphorylation dynamics in cancer may help improve existing and/or develop new therapies. Amata et al. (2014) report the interesting case of the role of phosphorylation events in the Unique domain of Src family kinases (SFKs). This domain, an intrinsically disordered region little conserved across the family and linking the kinase to its membrane-anchoring domain, is stubbed with phosphosites involved in multilevel regulation of SFKs, including, among others, anchoring to the lipid membrane. These examples hint at the high complexity of the cellular networks regulated by phospho-rylation. Kinases and phosphatases can be also regulated by phosphorylation and most of signal transduction pathways involve cascades of phosphorylation and de-phosphorylation events. This scenario should give the …