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bioRxiv · 10.1101/191684

Dephosphorylation is the Mechanism of Fibroblast Growth Factor Inhibition of Guanylyl Cyclase-B

Robinson, J. W.·Egbert, J. R.·Davydova, J.·Schmidt, H.·Jaffe, L. A.·Potter, L. R.
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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.\n\nHighlightsO_LIGuanylyl Cyclase-B is expressed in rat chondrosarcoma cells\nC_LIO_LIFGF2 induces a rapid, potent, and reversible inhibition of GC-B\nC_LIO_LIFGF2 treatment causes GC-B dephosphorylation\nC_LIO_LIFGF2 does not inhibit a dephosphorylation-resistant form of GC-B\nC_LIO_LIDephosphorylation is the mechanism of FGF2-dependent inhibition of GC-B\nC_LI\n\nAbbreviations

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Robinson, J. W., Egbert, J. R., Davydova, J., Schmidt, H., Jaffe, L. A., Potter, L. R.. 2017-09-20. Dephosphorylation is the Mechanism of Fibroblast Growth Factor Inhibition of Guanylyl Cyclase-B. https://doi.org/10.1101/191684

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