RT Journal Article
SR Electronic
T1 Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 193847
DO 10.1101/193847
A1 Leia C. Shuhaibar
A1 Jerid W. Robinson
A1 Ninna P. Shuhaibar
A1 Jeremy R. Egbert
A1 Giulia Vigone
A1 Valentina Baena
A1 Deborah Kaback
A1 Siu-Pok Yee
A1 Robert Feil
A1 Melanie C. Fisher
A1 Caroline N. Dealy
A1 Lincoln R. Potter
A1 Laurinda A. Jaffe
YR 2017
UL http://biorxiv.org/content/early/2017/09/28/193847.abstract
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.