Cloning and expression of guanylin. Its existence in various mammalian tissues.

Schulz, Stephanie; Chrisman, Ted D.; Garbers, D L

doi:10.1016/s0021-9258(18)41955-2

Cited by 120 publications

(8 citation statements)

References 23 publications

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“…Also, ST binding activity in cells which is not associated with guanylyl cyclase activation or GCC expression has been described (Hugues et al, 1992;Hirayama et al, 1992;Hakki et al, 1993b;Mann et al, 1993;Almenoff et al, 1994). In addition, ST may induce responses in extraintestinal organs, such as kidney, in which GCC is not expressed, suggesting that other receptors to which that peptide binds may exist (Lima et al, 1992;Schulz et al, 1992). Furthermore, atrial natriuretic peptides, which bind to members of the membrane receptorguanylyl cyclase family of proteins, guanylyl cyclases A and B, also bind to other receptors which are different gene products and not coupled to guanylyl cyclase (Garbers & Lowe, 1994).…”

Section: Discussionmentioning

confidence: 99%

Rat Guanylyl Cyclase C Expressed in COS-7 Cells Exhibits Multiple Affinities for Escherichia coli Heat-Stable Enterotoxin

Deshmane

Carrithers²,

Parkinson³

et al. 1995

Biochemistry

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Intestinal cells exhibit binding sites with different affinities for Escherichia coli heat-stable enterotoxin (ST) and guanylin, suggesting the existence of different receptors for these peptides. Guanylyl cyclase C from intestinal cells has been identified as one receptor for these peptides. Equilibrium and kinetic binding characteristics of rat guanylyl cyclase C expressed in COS-7 cells were examined, employing ST, to determine if this receptor exhibited multiple affinities. Scatchard analysis of equilibrium binding yielded curvilinear isotherms consistent with the presence of high (pM) and low (nM) affinity sites. Kinetic analysis of binding demonstrated that these sites exhibited similar dissociation but different association kinetics. In addition, two distinct affinity states of low affinity sites were identified with dissociation constants of 0.15 and 5.85 nM. Association of ST and low affinity sites was biphasic, while dissociation from these sites was unimodal. Close agreement of equilibrium and kinetic dissociation constants suggested that low affinity sites were in the lowest affinity state at equilibrium. Comparison of the ligand dependence of guanylyl cyclase activity (EC50 = 110 nM) with receptor occupancy revealed that binding of ST to the lowest affinity state of low affinity sites (EC50 = 80 nM) is directly coupled to catalytic activation. These studies suggest that binding sites with different affinities for ST exhibited by intestinal cells reflect the expression of a single gene product, guanylyl cyclase C, rather than different receptors for the ligand. The shift in affinity state of low affinity sites and its correlation with catalytic activation suggest a central role for this phenomenon in mechanisms mediating receptor-effector coupling of membrane guanylyl cyclases.

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Section: Discussionmentioning

confidence: 99%

Rat Guanylyl Cyclase C Expressed in COS-7 Cells Exhibits Multiple Affinities for Escherichia coli Heat-Stable Enterotoxin

Deshmane

Carrithers²,

Parkinson³

et al. 1995

Biochemistry

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“…Guanylin and uroguanylin were originally isolated from intestinal mucosa and urine, respectively (1,2,8). Northern blot analysis indicates that guanylin occurs not only in intestinal tissue but also in a variety of other tissues, such as kidney, airway epithelia, pancreas, and liver, while uroguanylin occurs in the intestine, atrium, and ventricle (9). Recently, another endogenous ligand of GC-C has been isolated from human blood and identified as a form of uroguanylin which is extended at the N terminus (Figure 1).…”

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confidence: 99%

In Vitro Disulfide-Coupled Folding of Guanylyl Cyclase-Activating Peptide and Its Precursor Protein

et al. 1998

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Guanylyl cyclase-activating peptide II (GCAP-II), an endogenous ligand of particulate guanylyl cyclase C (GC-C), is processed from the precursor protein and circulates in human blood. GCAP-II consists of 24 amino acid residues and contains two disulfide bridges. The correct disulfide paring of GCAP-II is an absolute requirement for its biological activity. This study shows that the folding of the peptide from the reduced form yields a peptide with the native disulfide paring as a minor product and with non-native ones as major products, regardless of the presence or absence of reduced and oxidized glutathione. The results suggest that GCAP-II does not possess sufficient information to permit the adoption of the native conformation and to effectively form the correct disulfide pairing and, as a result, that GCAP-II is correctly folded by assistance of a factor(s) such as an intra- or intermolecular chaperone. We studied whether a peptide in the pro-leader sequence of the precursor protein (proGCAP-II) contains sufficient information to facilitate the folding of GCAP-II. For this purpose, we prepared proGCAP-II in Escherichia coli by a recombinant technique and examined the disulfide-coupled folding of proGCAP-II from the reduced form. proGCAP-II was quantitatively recovered with the correctly folded structure from the reduced form both in the presence and in the absence of reduced and oxidized glutathione. The protein contains only disulfide linkages at the same positions as the mature form of proGCAP-II, GCAP-II, and the biologically active isomer of GCAP-II in the molecule. These results provide evidence that the propeptide of proGCAP-II is a critical factor in the formation of the correct disulfide paring in the folding of the protein.

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“…The mRNA for STaR is predicted to encode a protein of ∼120 kDa with the N-terminal ligand binding domain on the cell surface (Schulz et al, 1990). Northern analysis of STaR demonstrates a single 3.7 kb mRNA species, without evidence for alternative splicing (Schulz et al, 1990(Schulz et al, , 1992. Surprisingly, ligand affinity cross-linking studies of STaR have demonstrated several species of ST binding proteins, ranging in size from ∼50 to 160 kDa (Cohen et al, 1993;Hakki et al, 1993;Hirayama et al, 1992;Ivens et al, 1990;Katwa et al, 1991;Vaandrager et al, 1993Vaandrager et al, , 1994.…”

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confidence: 99%

Biogenesis, Cellular Localization, and Functional Activation of the Heat-Stable Enterotoxin Receptor (Guanylyl Cyclase C)

1996

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Enterotoxigenic Escherichia coli elaborate a peptide called heat-stable enterotoxin (ST), which binds to and activates the intestinal ST receptor (STaR). STaR, also known as guanylyl cyclase C (GC-C), is a member of the transmembrane guanylyl cyclase receptor family. The mRNA for STaR encodes an approximately 120 kDa protein with the N-terminal ligand binding domain on the cell surface. Ligand affinity cross-linking studies have previously demonstrated several species of potential ST binding proteins, ranging in size from approximately 50 to 160 kDa. Although these smaller forms of STaR (50-80 kDa) have been proposed to act in vivo as toxin binding proteins, their biogenesis and localization have not previously been examined. Using pulse labeling in vivo and synchronized translation in vitro, we demonstrate that these smaller forms represent incomplete translational products and are not formed through limited proteolysis of the full-length receptor, as had previously been believed. We determined, using fluorescence confocal microscopy and surface labeling, that only approximately 25% of cellular receptors are expressed at the surface, while the remaining population is retained within the endoplasmic reticulum. Only full-length receptor is found at the surface of the cell, indicating this to be the biologically active form of STaR responsible for interacting with the heat-stable enterotoxin and other luminal intestinal peptides. The large intracellular receptor population, and potential for function before translocation to the cell surface, may impact on how pharmacologic modulators of this clinically important receptor are designed.

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Cloning and expression of guanylin. Its existence in various mammalian tissues.

Cited by 120 publications

References 23 publications

Rat Guanylyl Cyclase C Expressed in COS-7 Cells Exhibits Multiple Affinities for Escherichia coli Heat-Stable Enterotoxin

Rat Guanylyl Cyclase C Expressed in COS-7 Cells Exhibits Multiple Affinities for Escherichia coli Heat-Stable Enterotoxin

In Vitro Disulfide-Coupled Folding of Guanylyl Cyclase-Activating Peptide and Its Precursor Protein

Biogenesis, Cellular Localization, and Functional Activation of the Heat-Stable Enterotoxin Receptor (Guanylyl Cyclase C)

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