TY - JOUR T1 - Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor JF - bioRxiv DO - 10.1101/193847 SP - 193847 AU - Leia C. Shuhaibar AU - Jerid W. Robinson AU - Ninna P. Shuhaibar AU - Jeremy R. Egbert AU - Giulia Vigone AU - Valentina Baena AU - Deborah Kaback AU - Siu-Pok Yee AU - Robert Feil AU - Melanie C. Fisher AU - Caroline N. Dealy AU - Lincoln R. Potter AU - Laurinda A. Jaffe Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/09/28/193847.abstract N2 - Activating mutations in fibroblast growth factor (FGF) receptor 3 and inactivating mutations in the NPR2 guanylyl cyclase cause similar forms of dwarfism, but how these two signaling systems interact to regulate bone growth is poorly understood. Here, by use of a mouse model in which NPR2 cannot be dephosphorylated, we show that bone elongation is opposed when NPR2 is dephosphorylated and thus produces less cyclic GMP. By developing an in vivo imaging system to measure cyclic GMP levels in intact tibia, we show that FGF-induced dephosphorylation of NPR2 decreases its guanylyl cyclase activity in growth plate chondrocytes in living bone. Thus FGF signaling lowers cyclic GMP in the growth plate, which counteracts bone elongation. These results define a new component of the signaling network by which activating mutations in the FGF receptor inhibit bone growth. ER -