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Review
. 2006 Aug;17(6):251-8.
doi: 10.1016/j.tem.2006.06.006. Epub 2006 Jun 30.

Membrane guanylyl cyclase receptors: an update

David L Garbers  1 , Ted D Chrisman, Phi Wiegn, Takeshi Katafuchi, Joseph P Albanesi, Vincent Bielinski, Barbara Barylko, Margaret M Redfield, John C Burnett Jr
Affiliations
Review

Membrane guanylyl cyclase receptors: an update

David L Garbers et al. Trends Endocrinol Metab. 2006 Aug.

Abstract

Recent studies have demonstrated key roles for several membrane guanylyl cyclase receptors in the regulation of cell hyperplasia, hypertrophy, migration and extracellular matrix production, all of which having an impact on clinically relevant diseases, including tissue remodeling after injury. Additionally, cell differentiation, and even tumor progression, can be profoundly influenced by one or more of these receptors. Some of these receptors also mediate important communication between the heart and intestine, and the kidney to regulate blood volume and Na+ balance.

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Figures

Figure 1
Figure 1
The conserved regulatory phosphorylation module of GCA and GCB. Despite the high similarity between the regulatory regions, GCB can be desensitized specifically by S1P and various growth factors. Abbreviations: PPi, inorganic pyrophosphate; TM, transmembrane segment.
Figure 2
Figure 2
Selective desensitization of GCB by serum. NIH–3T3 cell lines over-expressing rat GCA (GCA/3T3) or rat GCB (GCB/3T3) were serum starved for 24 -hours and then incubated in the absence (control) or presence of 1% fetal bovine serum (serum) for 30 minutes, followed by the addition of 20 nM ANP (GCA/3T3) or 20 nM CNP (GCB/3T3) for 5 minutes. Cyclic GMP (cGMP) contents were determined by radioimmunoassay. Inset: pERK in companion wells (A, GCA/3T3; B, GCB/3T3) were analyzed by western blotting after 5 minutes in the absence (c) or presence of 1% fetal bovine serum (ser). The results show that GCB is specifically desensitized to ligand stimulation by the addition of serum.
Figure 3
Figure 3
A model for the specific desensitization of GCB by S1P. The five putative receptors for S1P include three (S1P1, S1P2, S1P3) that are expressed in fibroblasts. The desensitization of GCB by S1P is insensitive to pertussis toxin, apparently eliminating Giα as a component of the desensitization pathway. Given that S1P1 has been suggested to signal through Gi, this receptor would then be eliminated as an element within the GCB desensitization pathway. This suggests that either the S1P2 or S1P3 receptor, or both, mediate S1P-specific desensitization of GCB. Abbreviations: AC, adenylyl cyclase; DAG, diacylglycerol; IP3, inositol trisphosphate; PI3K, phosphatidylinositol 3-kinase; MAPK, mitogen-activated protein kinase; PKC, protein kinase C; PLC, phospholipase C; SRF, serum response factor.
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