Novel secretory kinases regulate extracellular protein phosphorylation and biomineralization
报告人：Dr. Jixin CUI
Assistant Project Scientist, University of California at San Diego
地 点：金光生科大楼 Rm.411
Reversible phosphorylation is a fundamental mechanism used to regulate cellular signaling and protein function. In the past several decades, efforts have been focused on understanding phosphorylation events in the cytoplasm and nucleus. However, little is known about protein phosphorylation within the secretory pathway and outside the cells. Recently a family of unique secretory kinases has been discovered. The archetypical member, Fam20C, is the long-sought “Golgi casein kinase”, which phosphorylates many secreted proteins and is critical for proper formation of the bones and teeth. Fam20A, a Fam20C paralog, is essential for tooth enamel formation, but the biochemical function of Fam20A is unknown. Using a combination of biochemistry, structure biology and genome editing approaches, we demonstrate that Fam20A lacks a residue critical for catalysis and therefore is a pseudokinase. Nevertheless, Fam20A forms a functional complex with Fam20C and allosterically potentiates Fam20C kinase activity, promoting the phosphorylation of secretory proteins, including those forming the enamel matrix. These findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation.