Motif Analysis of Phosphosites Discloses a Potential Prominent Role of the Golgi Casein Kinase (GCK) in the Generation of Human Plasma Phospho-Proteome

By comparing the recurrent features of sequences surrounding 86 Ser/Thr residues phosphorylated in peptides from human plasma collected from literature with those generated from the whole human phosphoproteome, and from repertoires of validated substrates of the acidophilic protein kinases CK2 and Golgi casein kinase (GCK), the following conclusions can be drawn: (i) the contribution of Pro-directed and basophilic kinases to the plasma phosphoproteome is negligible, if any, while the contribution of acidophilic kinases is by far predominant; (ii) the plasma weblogo profile is closely reminiscent of that generated by GCK in its substrates, while it neatly differentiates from that generated by CK2; (iii) 58 plasma phosphosites out of 86 display the canonical consensus for GCK (S/T-x-E/pS), while that for CK2 (S/T-x-x-E/D/pS) is found in 15 peptides, all of which also conform to the GCK signature. These observations, in conjunction with a very similar situation disclosed by analyzing the phosphopeptides of the human cerebrospinal fluid collected from literature, support the view that GCK may play a major role in the phosphorylation of proteins secreted into body fluids.