Premium
The Golgi ‘casein kinase’ Fam20C is a genuine ‘phosvitin kinase’ and phosphorylates polyserine stretches devoid of the canonical consensus
Author(s) -
Cozza Giorgio,
Moro Enrico,
Black Miles,
Marin Oriano,
Salvi Mauro,
Venerando Andrea,
Tagliabracci Vincent S.,
Pinna Lorenzo A.
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14689
Subject(s) - phosvitin , phosphorylation , casein kinase 1 , phosphoprotein , kinase , biology , biochemistry , casein kinase 2 , phosphopeptide , protein phosphorylation , protein kinase a , microbiology and biotechnology , cyclin dependent kinase 2
Egg yolk phosvitins, generated through the fragmentation of vitellogenins (VTGs), are among the most heavily phosphorylated proteins ever described. Despite the early discovery in 1900 that chicken phosvitin is a phosphoprotein and its subsequent employment as an artificial substrate for a number of protein kinases, the identity of the enzyme(s) responsible for its phosphorylation remained a matter of conjecture until present. Here, we provide evidence that phosvitin phosphorylation is catalyzed by a family with sequence similarity 20, member C (Fam20C), an atypical protein kinase recently identified as the genuine casein kinase and responsible for the phosphorylation of many other secreted proteins at residues specified by the S‐x‐E/ pS consensus. Such a conclusion is grounded on the following observations: (a) the levels of Fam20C and phosphorylated VTG rise in parallel upon treatment of zebrafish with oestrogens; (b) zebrafish phosvitin is readily phosphorylated upon coexpression in U2 OS cells with Fam20C, but not with its catalytically inactive mutant; (c) a peptide reproducing a stretch of 12 serines, which are phosphorylated in chicken phosvitin despite lacking the C‐terminal priming motif S‐x‐E, is efficiently phosphorylated by both recombinant and native Fam20C. The last finding expands the repertoire of potential targets of Fam20C to include several proteins known to harbor (p‐Ser)n clusters not specified by any known kinase consensus.