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Our research focuses on the natriuretic peptide family and their cognate receptors, guanylyl cyclase-A (GC-A) and GC-B (Fig. 1). Both receptors are single membrane-spanning enzymes that consist of an extracellular ligand binding domain and intracellular kinase homology regulatory domain and cGMP synthesizing GC domain. Atrial natriuretic peptide (ANP) and brain natriuretic peptide decrease blood pressure and inhibit cardiac hypertrophy by activating GC-A. C-type natriuretic peptide (CNP) activation of GC-B regulates oocyte meiosis and stimulates long bone growth.Initial studies on post translational modifications of these enzymes indicated that phosphorylation and dephosphorylation are required for receptor activation and inactivation, respectively (Potter and Garbers, JBC, 1992, Potter, Biochemistry, 1998, Potter and Hunter, MCB, 1998, Potter and Hunter, JBC, 1998). Subsequent studies demonstrated that hormones that antagonize the actions of natriuretic peptides reduce signaling through this pathway by stimulating natriuretic peptide receptor dephosphorylation (Abbey and Potter, JBC, 2002, Abbey-Hosch et. al, Hypertension, 2004, Potthast et al, JBC, 2004). Later, we determined that GC-A, but not GC-B, is inactivated in failed murine and human hearts (Dickey et. al, Endocrinology, 2007, Dickey et. al, JMCC, 2013). We also found that N-linked glycosylation, another post-translational modification, is required for GC-B signaling and that missense mutation that inhibit glycosylation of GC-B cause dwarfism (Dickey et. al, JBC, 2016).Phosphomimetic forms of GC-A and GC-B that cannot be inactivated by dephosphorylation were engineered (Yoder et al. PLoS One, 2012, Otto et al, Mol. Pharmacol, 2017). In collaboration with Dr. Laurinda Jaffe's group, we produced mice expressing glutamate-substituted natriuretic peptide receptors that cannot be inactivated by dephosphorylation.
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Endocrine reviewsno. 5 (2024): 755-771
JOURNAL OF TRANSLATIONAL MEDICINEno. SUPPL 1 (2023)
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JOURNAL OF TRANSLATIONAL MEDICINEno. SUPPL 1 (2023)
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British journal of pharmacologyno. 24 (2023): 3254-3270
Calcified tissue internationalno. 5 (2022): 506-518
Stephen P. H. Alexander,Doriano Fabbro,Eamonn Kelly,Alistair Mathie,John A. Peters,Emma L. Veale,Jane F. Armstrong,Elena Faccenda,Simon D. Harding,Adam J. Pawson,Christopher Southan,Jamie A. Davies,Annie Beuve,Peter Brouckaert,Clare Bryant,John C. Burnett,Richard W. Farndale,Andreas Friebe,John Garthwaite,AdrianJ Hobbs,Gavin E. Jarvis,Michaela Kuhn,David MacEwan,Tom P. Monie,Andreas Papapetropoulos,Lincoln R. Potter,Harald H. H. W. Schmidt,Csaba Szabo,Scott A. Waldman
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#Papers: 120
#Citation: 7441
H-Index: 41
G-Index: 86
Sociability: 6
Diversity: 3
Activity: 12
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