PT  - JOURNAL ARTICLE
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
TI  - Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor
AID  - 10.1101/193847
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 193847
4099  - http://biorxiv.org/content/early/2017/09/28/193847.short
4100  - http://biorxiv.org/content/early/2017/09/28/193847.full
AB  - 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.