Protein Kinase A Anchoring Proteins Are Required for
Vasopressin-mediated Translocation of Aquaporin-2 into Cell
Membranes of Renal Principal Cells*
Enno
Klussmann
§,
Kenan
Maric
,
Burkhard
Wiesner
,
Michael
Beyermann
, and
Walter
Rosenthal
¶
From the
Forschungsinstitut für Molekulare
Pharmakologie, Alfred-Kowalke-Strasse 4, D-10315 Berlin,
Germany and the ¶ Freie Universität Berlin, Institut
für Pharmakologie, Thielallee 67-73, D-14195 Berlin,
Germany
 |
ABSTRACT |
The antidiuretic hormone arginine-vasopressin
(AVP) regulates water reabsorption in renal collecting duct principal
cells by inducing a cAMP-dependent translocation of water
channels (aquaporin-2, AQP-2) from intracellular vesicles into the
apical cell membranes. In subcellular fractions from primary cultured
rat inner medullary collecting duct (IMCD) cells, enriched for
intracellular AQP-2-bearing vesicles, catalytic protein kinase A (PKA)
subunits and several protein kinase A anchoring proteins (AKAPs) were
detected. In nonstimulated IMCD cells the majority of AQP-2 staining
was detected intracellularly but became mainly localized within the
cell membrane after stimulation with AVP or forskolin. Quantitative
analysis revealed that preincubation of the cells with the synthetic
peptide S-Ht31, which prevents the binding between AKAPs and regulatory subunits of PKA, strongly inhibited AQP-2 translocation in response to
forskolin. Preincubation of the cells with the PKA inhibitor H89 prior
to forskolin stimulation abolished AQP-2 translocation. In contrast to
H89, S-Ht31 did not affect the catalytic activity of PKA. These data
demonstrate that not only the activity of PKA, but also its tethering
to subcellular compartments, are prerequisites for
cAMP-dependent AQP-2 translocation.
 |
INTRODUCTION |
The antidiuretic action of arginine-vasopressin
(AVP)1 is mediated by renal
collecting duct principal cells. The water channel aquaporin-2 (AQP-2),
which is exclusively expressed in principal cells, belongs to a family
of water channel proteins (aquaporins), which greatly increase the
osmotic water permeability of biological membranes (1, 2). In resting
principal cells AQP-2 is localized on intracellular vesicles. The
antidiuretic hormone AVP causes its redistribution from the
intracellular compartment to the apical cell membrane and thereby
facilitates water reabsorption (3, 4). Mutations in the genes coding
for the vasopressin V2 receptor or AQP-2 cause nephrogenic diabetes
insipidus, a disease characterized by a massive loss of water through
the kidney (5-9).
The binding of AVP to vasopressin V2 receptors (10) on principal cells
stimulates cAMP synthesis via the Gs/adenylyl cyclase system. Cyclic AMP activates protein kinase A (PKA), which in turn
phosphorylates AQP-2 at Ser-256 (11, 12). The functional consequence of
this modification is not clear: Kuwahara et al. (11) found a
minor increase in AQP-2 water permeability in oocytes injected with
AQP-2 mRNA, while Lande et al. (13) did not find an
increased water permeability in isolated AQP-2-bearing vesicles after
phosphorylation. Elimination of the PKA phosphorylation site of AQP-2
or incubation with the PKA inhibitor H89 prevents AQP-2 translocation
in LLC-PK1 cells stably transfected with the water channel (14). These
data indicate that the phosphorylation of AQP-2 is important for its
subcellular localization rather than for its function. The finding that
isolated AQP-2-bearing vesicles contain endogenous PKA activity (13)
led to the premise that PKA might be anchored to the vesicle membranes
by protein kinase A anchoring proteins (AKAPs), whose function is to
localize PKA in close proximity to its substrates (15-19). In the
present work it was investigated whether the compartmentalization of
PKA by AKAPs is obligatory for AQP-2 translocation. A recently
described primary cell culture model of rat IMCD cells (20) was
utilized to address this question.
 |
EXPERIMENTAL PROCEDURES |
Preparation of Peptides--
The synthetic peptide Ht31, derived
from the human AKAP Ht31 (residues 493-515; Ref. 21), assumes an
amphipathic helix structure that binds regulatory PKA subunits. This
inhibits binding of regulatory PKA subunits to AKAPs and consequently
the tethering of PKA to subcellular compartments. The inactive control
peptide Ht31-P, containing prolines at positions 502 and 507, does not
assume the amphipathic helix structure and therefore cannot prevent
binding of PKA regulatory subunits to AKAPs. For detection of AKAPs
with radioactive regulatory RII subunits of PKA in RII overlay
experiments, Ht31 and Ht31-P were used without stearate. S-Ht31 and
S-Ht31-P are coupled to stearate residues and thus rendered
membrane-permeable (22); these peptides were used in experiments with
intact IMCD cells. All peptides, including AVP, were synthesized on a
433A peptide synthesizer (Applied Biosystems, Weiterstadt, Germany) on
Rapp resin columns (Rapp Polymere, Tuebingen, Germany) using Fmoc
(N-(9-fluorenyl)methoxycarbonyl) chemistry. Stearic acid was
added to the free N terminus of the protected peptides before cleavage
from the resin. The peptides were purified and analyzed by high
performance liquid chromatography on Polyencap A300 columns (Bischoff,
Leonberg, Germany) and electrospray mass spectrometry (TSQ 700, Finnigan MAT, Bremen, Germany).
Primary Cell Culture of Rat IMCD Cells--
IMCD cells were
cultured in the presence of dibutyryl cAMP as described (20). Dibutyryl
cAMP was removed 16 h before experimental analyses, which were
performed 6 days after seeding. The cells were incubated with synthetic
peptides (S-Ht31 and S-Ht31-P) or the PKA inhibitor H89 (Calbiochem,
Bad Soden, Germany) as indicated.
Immunofluorescence Microscopy and Quantification of
Immunofluorescence Intensities--
AQP-2 was visualized by
immunofluorescence microscopy as described (20, 23). Fluorescence
signals (xy images) were detected by confocal microscopy with a laser
scanning microscope (LSM 410; Carl Zeiss, Jena, Germany). For
quantification the immunofluorescence and transmission images of each
cell were scanned with the confocal microscope. These two images were
used for determination of the intracellular and cell membrane
fluorescence signal intensities with an image analysis software (KS400,
Kontron Electronic). Cytosol, cell membranes, and nuclei of each cell
were marked on the transmission image. The masks obtained were
transferred to the immunofluorescence images and immunofluorescence
signal intensities were measured in the marked areas. Intracellular and
cell membrane signal intensities were related to the signal intensity
of the nucleus (subtraction of unspecific immunofluorescence signals
derived from the secondary antibody). Then the intracellular:cell
membrane signal intensity ratios were calculated. For all groups mean
and S.E. values were calculated. Statistically significant differences
were determined using the Student's t test and one way
analysis of variance. In addition to xy scans, z scans were carried out
to investigate the fluorescence at different levels in z direction.
Preparation of IMCD Cell Fractions Enriched for Cell Membranes or
Intracellular Vesicles, Western Blotting, and Detection of
AKAPs--
IMCD cells were either untreated or stimulated with AVP (1 µM). Fractions enriched for cell membranes (low speed
pellet (LS), 17,000 × g) or intracellular vesicles
(high speed pellet (HS), 200,000 × g) were prepared as
described (24, 25). AQP-2 was detected by Western blot with the
antiserum H27 (1:5,000; Ref. 20). Catalytic PKA subunits were detected
with a specific antiserum kindly provided by Dr. G. Schwoch (1:4,000;
University of Göttingen, Germany; Refs. 20 and 26). Alkaline
phosphatase-conjugated goat anti-rabbit IgG (Dianova, Hamburg, Germany)
was used as secondary antibody (1:2,500). AKAPs were detected by the
RII overlay procedure described previously (27). The overlays were
carried out in the presence of either the active peptide Ht31 (10 µM) or the control peptide Ht31-P (10 µM;
see above).
Phosphorylation of Membrane Proteins with
[
-32P]ATP--
HS pellets (25 µg; see above) were
resuspended in phosphate-buffered saline and incubated in the presence
of [
-32P]ATP (0.1 mM, 10 Ci/mmol; NEN Life
Science Products, Köln, Germany) and exogenous catalytic PKA
subunits (20 units/ml; Promega, Mannheim, Germany; Ref. 13). H89,
Me2SO, or synthetic peptides were added as indicated. The
proteins were separated by 10% SDS-PAGE. Radioactive proteins were
detected by autoradiography.
 |
RESULTS |
Disruption of the Binding between PKA and AKAPs or Inhibition of
PKA Prevents AQP-2 Translocation to the Cell Membranes of Rat IMCD
Cells--
Rat IMCD cells were cultured for 6 days as described (20).
Prior to stimulation with AVP (1 µM, 30 min) or forskolin
(100 µM, 15 min), they were incubated with the
membrane-permeable peptide S-Ht31 (100 µM, 30 min), which
inhibits the binding of PKA to AKAPs, or with the corresponding
(inactive) control peptide S-Ht31-P (100 µM, 30 min).
Subsequently, the distribution of AQP-2 was determined by
immunofluorescence microscopy. Fig.
1A shows a mainly intracellular distribution of AQP-2 in nonstimulated control cells. After stimulation of the cells with forskolin (Fig. 1B), the
AQP-2 staining was mainly present at the basolateral cell membranes as
shown by both xy and z scans (20). Preincubation of the cells with
S-Ht31 prior to forskolin stimulation strongly inhibited this
redistribution (Fig. 1C), whereas preincubation with the control peptide S-Ht31-P inhibited the redistribution of AQP-2 only
weakly (Fig. 1D). Preincubation with the PKA inhibitor H89 abolished AQP-2 redistribution (Fig. 1E). To quantify the
effect of the synthetic peptides and of H89, intracellular and cell
membrane fluorescence signal intensities were related to nuclear
fluorescence signal intensities by laser scanning microscopy (Fig.
2A), and the ratios of
intracellular/cell membrane fluorescence signal intensities were
determined (Fig. 2B; see "Experimental Procedures"). Fig. 2B shows two groups of ratios: ratios > 1 were
determined for nonstimulated control cells (1.77 ± 0.08;
mean ± S.E.) and for forskolin-stimulated cells preincubated with
H89 (1.75 ± 0.05) or S-Ht31 (1.58 ± 0.06), indicating a
primarily intracellular location of AQP-2. Ratios < 1 were
determined for forskolin-stimulated cells (0.31 ± 0.02) and for
cells preincubated with S-Ht31-P (0.60 ± 0.05) prior to forskolin
stimulation, indicating a predominant localization of AQP-2 at the cell
membrane. The ratios obtained for nonstimulated cells and
forskolin-stimulated cells preincubated with H89 or S-Ht31 were
significantly higher than those for forskolin-stimulated cells with or
without S-Ht31-P preincubation. Preincubation with the control peptide
S-Ht31-P partially inhibited AQP-2 translocation, probably due to
inhibition of PKA (see below). These results demonstrate that not only
the catalytic activity of PKA, but also its tethering to subcellular
compartments via anchoring by AKAPs, are prerequisites for the AQP-2
translocation.

View larger version (68K):
[in this window]
[in a new window]
|
Fig. 1.
Localization of AQP-2 in primary cultured
IMCD cells. IMCD cells were incubated with or without synthetic
peptide or H89 for 30 min. If indicated, forskolin (100 µM) was added for a further 15 min. Thereafter cells were
fixed, permeabilized, and incubated with anti-AQP-2 antibodies and
secondary cy3-conjugated anti-rabbit antibodies. Immunofluorescence was
visualized by laser scanning microscopy (for details, see
"Experimental Procedures"). The upper part of each panel represents
xy and the lower part z scans derived from the cells marked by the
black line in the xy image. A, nonstimulated control cells.
B, cells stimulated with forskolin. C,
forskolin-stimulated cells preincubated with the membrane-permeable
peptide S-Ht31 (100 µM), which inhibits binding of PKA to
AKAPs. D, forskolin-stimulated cells preincubated with
S-Ht31-P (100 µM) control peptide. E,
forskolin-stimulated cells preincubated with the PKA inhibitor H89 (30 µM). z scans in A, C, and
E indicate a predominant intracellular localization of
AQP-2. The z scans in B and D demonstrate the
presence of AQP-2 mainly in the basolateral cell membrane.
|
|

View larger version (24K):
[in this window]
[in a new window]
|
Fig. 2.
Quantitative analysis of the effects of the
synthetic peptides S-Ht31 and S-Ht31-P and the PKA inhibitor H89 on
forskolin-induced AQP-2 translocation in IMCD cells. Cells were
treated as indicated in Fig. 1, A-E. Immunofluorescence
staining of AQP-2 was visualized and quantitatively analyzed by laser
scanning microscopy (for details, see "Experimental Procedures").
A, intracellular and cell membrane fluorescence signal
intensities were related to the nuclear fluorescence signal intensities
for 44 cells under each set of conditions (8-bit scale; mean ± S.E.; three independent experiments). B, the ratios of
intracellular/cell membrane fluorescence signal intensities were
calculated. Ratios > 1 indicate a predominantly intracellular
localization of AQP-2, and ratios < 1 a predominant
localization at the cell membrane. Statistically significant
differences (p < 0.05) between the ratios are given.
Differences between the ratios obtained for nonstimulated cells and
forskolin-stimulated cells preincubated with H89 or S-Ht31 were not
significantly different.
|
|
32P-Phosphorylation of the IMCD Cell Fraction Enriched
for Intracellular Vesicles in the Presence of S-Ht31, S-Ht31-P, Ht31,
Ht31-P, or the PKA Inhibitor H89--
To investigate the influence of
the synthetic peptides and of H89 on the catalytic activity of PKA,
in vitro phosphorylation assays were performed (Fig.
3). Endogenous protein kinase activity of
the HS fraction was very low (not shown). Addition of exogenous catalytic subunits of PKA led to the phosphorylation of various proteins. This effect was abolished by H89 (30 µM), but
appeared to be slightly enhanced in the presence of Me2SO
(1%), in which the peptides were dissolved. Incubations with the
peptides S-Ht31, Ht31 and Ht31-P in 10 or 100 µM
concentrations did not inhibit phosphorylation. S-Ht31-P did not
inhibit phosphorylation at a concentration of 10 µM, but,
similarly to H89, abolished phosphorylation at a concentration of 100 µM. The inhibitory effect of S-Ht31-P on PKA activity may
explain the partial inhibition of AQP-2 redistribution by this peptide
(Figs. 1 and 2).

View larger version (89K):
[in this window]
[in a new window]
|
Fig. 3.
Phosphorylation of proteins from fractions
enriched for intracellular vesicles with
[ -32P]ATP (13). IMCD cell
fractions enriched for intracellular vesicles (HS fraction, 25 µg)
were incubated with [ -32P]ATP in the presence of
exogenous catalytic PKA subunits. The proteins were separated by
SDS-PAGE, and the gel was autoradiographed (for details, see
"Experimental Procedures"). In addition to catalytic PKA subunits
the PKA inhibitor H89 (30 µM), Me2SO
(DMSO) (1%), in which synthetic peptides were dissolved or
the synthetic peptides S-Ht31, S-Ht31-P, Ht31, or Ht31-P were added to
the reaction mixture as indicated.
|
|
Detection of AQP-2 and Catalytic PKA Subunits in IMCD Cell
Fractions Enriched for Intracellular Vesicles or Cell
Membranes--
Western blotting was used to demonstrate the presence
of AQP-2 and catalytic PKA subunits in fractions from IMCD cells
enriched for either cell membranes (LS) or intracellular vesicles (HS; Fig. 4). Catalytic PKA subunits were
detected in both fractions, and no change in distribution between the
two fractions was observed after stimulation with AVP (
and + AVP in
Fig. 4) or forskolin (not shown). In contrast, the amount of AQP-2
decreased in the intracellular vesicle fraction after stimulation,
indicating a shift to the cell membrane as described previously
(20).

View larger version (37K):
[in this window]
[in a new window]
|
Fig. 4.
Detection of AQP-2 and catalytic PKA subunits
(cPKA) in IMCD cell fractions enriched for cell
membranes (LS) or intracellular vesicles
(HS). IMCD cells were left unstimulated or
stimulated with arginine-vasopressin (AVP; 1 µM) before
subcellular fractionation (24, 25). Proteins (30 µg/lane) were
separated by SDS-PAGE, blotted onto nitrocellulose, and glycosylated,
and nonglycosylated AQP-2 (upper and lower
bands, respectively) was detected with a specific antiserum (20,
29). Catalytic PKA subunits were detected with an antiserum kindly
provided by Dr. G. Schwoch (University Göttingen, Germany; Ref.
26).
|
|
Presence of AKAPs in IMCD Cell Fractions Enriched for Intracellular
Vesicles or Cell Membranes--
RII overlay assays of total IMCD cell
homogenate and subcellular fractions enriched for cell membranes (LS)
or intracellular vesicles (HS) with radioactively labeled RII subunits
were carried out (see "Experimental Procedures"). The overlay in
Fig. 5A was performed in the
presence of the control peptide Ht31-P (or in the absence of peptide,
not shown), and that in Fig. 5B in the presence of Ht31. The
remaining bands (55 kDa) in Fig. 5B probably represent
regulatory RII subunits. The peptide Ht31 inhibits all binding of the
radioactive RII subunits to the membrane-bound proteins, excepting the
55-kDa protein. Thus the bands visible in Fig. 5A represent
AKAPs. One AKAP (35 kDa) was found only in the fraction enriched for
cell membranes (LS) and several others (70-80, 95, and >120 kDa) only
in the fraction enriched for intracellular vesicles (HS). No change in
distribution of AKAPs between the two fractions was observed after
stimulation with AVP (
and + AVP in Fig. 5) or forskolin (not
shown).

View larger version (100K):
[in this window]
[in a new window]
|
Fig. 5.
Detection of AKAPs in subcellular IMCD cell
fractions. Total cell homogenates (lanes 1 and
4) and fractions enriched for cell membranes (LS,
lanes 2 and 5) or intracellular vesicles (HS,
lanes 3 and 6) were obtained from nonstimulated
or AVP-stimulated ( AVP and +AVP, 1 µM) IMCD cells (25).
Proteins (120 µg per lane) were separated by SDS-PAGE (10%) and
blotted onto nitrocellulose membranes. Regulatory RII subunits of PKA
were 32P-phosphorylated by incubation with
[ -32P]ATP and catalytic PKA subunits and hybridized to
the filter-bound proteins (27). A, the hybridization was
carried out in the presence the control peptide Ht31-P (10 µM). B, the hybridization was carried out in
the presence of the peptide Ht31, which inhibits the binding of
regulatory RII subunits to AKAPs (10 µM).
|
|
 |
DISCUSSION |
AKAPs are targeting proteins, which anchor PKA in close proximity
to its substrates (15-19). Membrane-permeable peptides (myristylated or stearated) comprising the amphipathic helix region of Ht31 (21)
effectively compete for PKA-AKAP interaction (17). These peptides have
been shown to relieve cAMP-dependent inhibition of
interleukin-2 transcription (17) and to arrest sperm motility (22). In
this study, synthetic Ht31-derived peptides coupled to stearic acid
(S-Ht31) were used to demonstrate that the targeting of PKA to
subcellular compartments via AKAPs is a prerequisite for cAMP-mediated
AQP-2 translocation (Figs. 1 and 2).
Incubation of primary cultured IMCD cells with S-Ht31 strongly
inhibited AQP-2 translocation, although less efficiently than incubation with the PKA inhibitor H89 (Fig. 2). The peptide, in contrast to H89, did not inhibit PKA activity in an in vitro
phosphorylation assay (Fig. 3). It is therefore highly unlikely that
S-Ht31 inhibits PKA activity in IMCD cells. A minor fraction of
intracellular AQP-2 may be phosphorylated by the nontethered, cytosolic
PKA which may explain why S-Ht31 inhibits translocation not completely, in contrast to H89. The control peptide S-Ht31-P did not inhibit PKA
activity at a low concentration (10 µM) in the in
vitro phosphorylation assay, but abolished the activity at the
concentration used for incubation of IMCD cells (100 µM,
Fig. 3). The apparent discrepancy between complete inhibition of PKA
activity in vitro and the small inhibitory effect of
S-Ht31-P on AQP-2 translocation in IMCD cells (Figs. 1 and 2) may arise
because the intracellular peptide concentration is most probably lower
than that of the growth medium. Therefore, inhibition of PKA appears
dependent on the amount of S-Ht31-P that actually enters the cell.
The finding that several different AKAPs and catalytic PKA subunits are
present in IMCD cell fractions enriched for intracellular vesicles (HS)
that contain AQP-2 is consistent with these proteins residing on the
same vesicles (Figs. 4 and 5). Since additional AKAPs were, however,
also found in the fraction enriched for cell membranes (LS; Fig. 5), it
is also possible that the AKAPs required for AQP-2 translocation are
present on other cellular compartments, like cell membranes or the cytoskeleton.
There was no decrease in the amount of catalytic PKA subunits or AKAPs
in the HS fraction after AVP stimulation, in contrast to AQP-2, which
redistributed to the cell membrane (Figs. 4 and 5). Furthermore, the
distribution of proteins of about 55 kDa, probably representing
regulatory PKA subunits, did not change after stimulation (Fig. 5). The
HS fractions may contain minor amounts of cytosol or particulate
subcellular compartments other than AQP-2-bearing vesicles, veiling
small differences in the distribution of PKA or AKAPs after stimulation
(for example in HEK293 cells 90% of PKA RII
- and
-subunits are
cytosolic (28)). On the other hand, no redistribution of other proteins
than AQP-2 to the cell membrane after stimulation of IMCD cells with
AVP or forskolin has been described to date, although a co-enrichment of AQP-2-bearing vesicles and Rab3 proteins (29) and the colocalization of AQP-2, synaptobrevin II, dynein, and dynactin on vesicles have been
demonstrated (30, 31, 32). Therefore, delivery of AQP-2 to the apical
cell membrane may possibly be followed by immediate recycling of other
vesicle-associated proteins.
Recently it was shown that PKA anchoring to AKAPs facilitates glucagon
like peptide-1-mediated insulin secretion in primary islets and RINm5F
cells (33), underlining the significance of PKA compartmentalization in
exocytosis. Members of the cytoskeleton-associated ERM family
(ezrin, radixin, and moesin) of
proteins (34) have been identified as AKAPs (35). Ezrin seems to be
directly involved in the control of gastric acid secretion by parietal
cells (35), a cAMP-dependent exocytosis analogous to the
translocation of AQP-2 in kidney principal cells. The expression of
ezrin in kidney collecting duct epithelium has been demonstrated (36),
and we recently showed the presence of moesin in principal cells (37). Ezrin and/or moesin might play a similar role in AQP-2 translocation to
that of ezrin in acid secretion. This possibility is being investigated
at present. Furthermore, we are attempting to identify the AKAPs
detected by the overlay technique in the IMCD cell fraction enriched
for intracellular vesicles. Vesicle-associated AKAPs may play a general
role in cAMP-dependent exocytotic events, including those
mentioned above, and also mast cell degranulation or thyroglobulin secretion.
 |
ACKNOWLEDGEMENTS |
We thank Dr. E. Krause (Forschungsinstitut
für Molekulare Pharmakologie, Berlin, Germany) for performing
mass spectrometric analysis of the synthetic peptides used in this
study and Dr. G. Schwoch (University of Göttingen, Germany) for
the antiserum against catalytic subunits of PKA. We are grateful to A. Geelhaar for excellent technical assistance and J. Dickson for
critically reading the manuscript.
 |
FOOTNOTES |
*
This work was supported by a grant from the Deutsche
Forschungsgemeinschaft (Ro 597/6).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
To whom correspondence should be addressed: Forschungsinstitut
für Molekulare Pharmakologie, Alfred-Kowalke-Str.-4, 10315 Berlin, Germany. Tel.: 49-30-51551-258; Fax: 49-30-51551-291; E-mail:
klussmann{at}fmp-berlin.de.
 |
ABBREVIATIONS |
The abbreviations used are:
AVP, arginine-vasopressin;
AQP-2, aquaporin-2;
IMCD, inner medullary
collecting duct;
AKAP, protein kinase A anchoring protein;
PKA, protein
kinase A;
RII, type II regulatory subunit of PKA;
H89, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide;
LS, low speed pellet;
HS, high speed pellet;
PAGE, polyacrylamide gel
electrophoresis.
 |
REFERENCES |
-
Agre, P.,
Brown, D.,
and Nielson, S.
(1995)
Curr. Opin. Cell Biol.
7,
472-483[CrossRef][Medline]
[Order article via Infotrieve]
-
Agre, P.,
Bonhivers, M.,
and Borgnia, M. J.
(1998)
J. Biol. Chem.
273,
14659-14662[Free Full Text]
-
Knepper, M.,
and Inoue, T.
(1997)
Curr. Opin. Cell Biol.
9,
560-564[CrossRef][Medline]
[Order article via Infotrieve]
-
Sasaki, S.,
Ishibashi, K.,
and Marumo, F.
(1998)
Annu. Rev. Physiol.
60,
199-220[CrossRef][Medline]
[Order article via Infotrieve]
-
Rosenthal, W.,
Seibold, A.,
Antaramian, A.,
Lonergan, M.,
Arthus, M.-F.,
Hendy, G.,
Birnbaumer, M.,
and Bichet, D.
(1992)
Nature
359,
233-235[CrossRef][Medline]
[Order article via Infotrieve]
-
Rosenthal, W.,
Oksche, A.,
and Bichet, D. G.
(1998)
Adv. Mol. Cell. Endocrinol.
2,
143-167
-
Oksche, A.,
and Rosenthal, W.
(1998)
J. Mol. Med.
76,
326-337[CrossRef][Medline]
[Order article via Infotrieve]
-
Deen, P. M. T.,
Verdijk, M. A. J.,
Knoers, N. V. A. M.,
Wieringa, B.,
Monnens, L. A. H.,
van Os, C. H.,
and van Oost, B. A.
(1994)
Science
264,
92-95[Medline]
[Order article via Infotrieve]
-
Deen, P. M. T.,
and Knoers, N. V. A. M.
(1998)
Curr. Opin. Nephrol. Hypertens.
7,
37-42[CrossRef][Medline]
[Order article via Infotrieve]
-
Birnbaumer, M.,
Seibold, A.,
Gilbert, S.,
Ishido, M.,
Barberis, B.,
Antaramian, A.,
Brabet, P.,
and Rosenthal, W.
(1992)
Nature
357,
333-335[CrossRef][Medline]
[Order article via Infotrieve]
-
Kuwahara, M.,
Fushimi, K.,
Terada, Y.,
Bai, L.,
Marumo, F.,
and Sasaki, S.
(1995)
J. Biol. Chem.
270,
10384-10387[Abstract/Free Full Text]
-
Fushimi, K.,
Sasaki, S.,
and Marumo, F.
(1997)
J. Biol. Chem.
272,
14800-14804[Abstract/Free Full Text]
-
Lande, M. B.,
Jo, I.,
Zeidel, M. L.,
Somers, M.,
and Harris, H. W.
(1996)
J. Biol. Chem.
271,
5552-5557[Abstract/Free Full Text]
-
Katsura, T.,
Gustafson, C. E.,
Ausiello, D. A.,
and Brown, D.
(1997)
Am. J. Physiol.
272,
F816-F822
-
Rubin, C. S.
(1994)
Biochim. Biophys. Acta
1224,
467-479[Medline]
[Order article via Infotrieve]
-
Faux, M. C.,
and Scott, J. D.
(1996)
Cell
85,
9-12[Medline]
[Order article via Infotrieve]
-
Lester, L. B.,
and Scott, J. D.
(1997)
Recent Prog. Horm. Res.
52,
409-430[Medline]
[Order article via Infotrieve]
-
Dell'Acqua, M. L.,
and Scott, J. D.
(1997)
J. Biol. Chem.
272,
12881-12884[Free Full Text]
-
Pawson, T.,
and Scott, J. D.
(1997)
Science
278,
2075-2080[Abstract/Free Full Text]
-
Maric, K.,
Oksche, A.,
and Rosenthal, W.
(1998)
Am. J. Physiol.
275,
F796-F801[Abstract/Free Full Text]
-
Carr, D. W.,
Hausken, Z. E.,
Fraser, I. D. C.,
Stofko-Hahn, R. E.,
and Scott, J. D.
(1992)
J. Biol. Chem.
267,
13376-13382[Abstract/Free Full Text]
-
Vijayaraghavan, S.,
Goueli, S. A.,
Davey, M. P.,
and Carr, D. W.
(1997)
J. Biol. Chem.
272,
4747-4752[Abstract/Free Full Text]
-
Oksche, A.,
Dehe, M.,
Schülein, R.,
Wiesner, B.,
and Rosenthal, W.
(1998)
FEBS Lett.
424,
57-62[CrossRef][Medline]
[Order article via Infotrieve]
-
Mandon, B.,
Chou, C.-L.,
Nielsen, S.,
and Knepper, M. A.
(1996)
J. Clin. Invest.
98,
906-913[Abstract/Free Full Text]
-
Marples, D.,
Knepper, M. A.,
Christensen, E. I.,
and Nielsen, S.
(1995)
Am. J. Physiol.
269,
C655-C664[Abstract]
-
Schwoch, G.,
Hamann, A.,
and Hilz, H.
(1980)
Biochem. J.
192,
223-230[Medline]
[Order article via Infotrieve]
-
Bregman, D. B.,
Bhattacharyya, N.,
and Rubin, C. S.
(1989)
J. Biol. Chem.
264,
4648-4656[Abstract/Free Full Text]
-
Ndubuka, C.,
Li, Y.,
and Rubin, C. S.
(1993)
J. Biol. Chem.
268,
7621-7624[Abstract/Free Full Text]
-
Liebenhoff, U.,
and Rosenthal, W.
(1995)
FEBS Lett.
365,
209-213[CrossRef][Medline]
[Order article via Infotrieve]
-
Jo, I.,
Harris, H. W.,
Amendt-Raduege, A. M.,
Majewski, R. R.,
and Hammond, T. G.
(1995)
Proc. Natl. Acad. Sci. U. S. A.
92,
1876-1880[Abstract]
-
Nielsen, S.,
Marples, D.,
Birn, H.,
Mohtashami, M.,
Dalby, N. O.,
Trimple, W.,
and Knepper, M.
(1995)
J. Clin. Invest.
96,
1834-1844[Medline]
[Order article via Infotrieve]
-
Marples, D.,
Schroer, T. A.,
Ahrens, N.,
Taylor, A.,
Knepper, M. A.,
and Nielsen, S.
(1998)
Am. J. Physiol.
274,
F384-F394[Abstract/Free Full Text]
-
Lester, L. B.,
Langeberg, L. K.,
and Scott, J. D.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
14942-14947[Abstract/Free Full Text]
-
Tsukita, S.,
Yonemura, S.,
and Tsukita, S.
(1997)
Curr. Opin. Cell Biol.
9,
70-75[CrossRef][Medline]
[Order article via Infotrieve]
-
Dransfield, D. T.,
Bradford, A. J.,
Smith, J.,
Martin, M.,
Roy, C.,
Mangeat, P. H.,
and Goldenring, J. R.
(1997)
EMBO J.
16,
35-43[Abstract/Free Full Text]
-
Bretscher, A.,
Reczek, D.,
and Berryman, M.
(1997)
J. Cell Sci.
110,
3011-3018[Abstract/Free Full Text]
-
Klussmann, E.,
Maric, K.,
Krause, E.,
Eichhorst, J.,
Beziat, P.,
and Rosenthal, W.
(1998)
J. Mol. Med.
76,
B58 (abstr.)
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.