Dephosphorylation is the mechanism of fibroblast growth factor inhibition of guanylyl cyclase-B.

Abstract

Activating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations of guanylyl cyclase-B (GC-B, also called NPRB or NPR2) cause dwarfism. FGF exposure inhibits GC-B activity in a chondrocyte cell line, but the mechanism of the inactivation is not known. Here, we report that FGF exposure causes dephosphorylation of GC-B in rat chondrosarcoma cells, which correlates with a rapid, potent and reversible inhibition of C-type natriuretic peptide-dependent activation of GC-B. Cells expressing a phosphomimetic mutant of GC-B that cannot be inactivated by dephosphorylation because it contains glutamate substitutions for all known phosphorylation sites showed no decrease in GC-B activity in response to FGF. We conclude that FGF rapidly inactivates GC-B by a reversible dephosphorylation mechanism, which may contribute to the signaling network by which activated FGFR3 causes dwarfism.

• Authors: Jerid W Robinson, Jeremy R Egbert, Julia Davydova, Hannes Schmidt, Laurinda A Jaffe, Lincoln R Potter
• Journal: Cellular signalling (Cell Signal) Vol. 40 Pg. 222-229 (12 2017) ISSN: 1873-3913 [Electronic] England
• PMID: 28964968 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Natriuretic Peptide, C-Type
• Glutamic Acid
• Receptor, Fibroblast Growth Factor, Type 3
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor B
• Cyclic GMP

Topics

• Animals
• Chondrocytes (metabolism)
• Cyclic GMP (genetics)
• Disease Models, Animal
• Dwarfism (genetics, metabolism, pathology)
• Glutamic Acid (metabolism)
• Humans
• Natriuretic Peptide, C-Type (genetics)
• Phosphorylation
• Rats
• Receptor, Fibroblast Growth Factor, Type 3 (genetics, metabolism)
• Receptors, Atrial Natriuretic Factor (genetics, metabolism)
• Signal Transduction