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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.

SUBMITTER: Robinson JW

PROVIDER: S-EPMC5651182 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Robinson Jerid W JW Egbert Jeremy R JR Davydova Julia J Schmidt Hannes H Jaffe Laurinda A LA Potter Lincoln R LR

Cellular signalling 20170928

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 ...[more]

PMID: 28964968

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