TY - JOUR TI - A secretory kinase complex regulates extracellular protein phosphorylation AU - Cui, Jixin AU - Xiao, Junyu AU - Tagliabracci, Vincent S AU - Wen, Jianzhong AU - Rahdar, Meghdad AU - Dixon, Jack E A2 - Hunter, Tony VL - 4 PY - 2015 DA - 2015/03/19 SP - e06120 C1 - eLife 2015;4:e06120 DO - 10.7554/eLife.06120 UR - https://doi.org/10.7554/eLife.06120 AB - Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our 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. KW - kinase complex KW - extracellular protein phosphorylation KW - secretory pathway phosphorylation KW - pseudokinase KW - tooth enamel formation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -