Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arginine vasopressin (AVP) is a nonapeptide that regulates body fluid and blood pressure homeostasis. We have used expression cloning in the Xenopus laevis oocyte system to identify cDNA clones from a rabbit renal medullary expression library encoding an AVP receptor linked to Ca2+ mobilization. cRNA generated from positive clones conferred upon oocytes the capacity to mobilize intracellular Ca2+ in response to AVP. A cDNA clone encoding a protein of 780 amino acids was isolated, sequenced, and subcloned into an SV40-based expression vector. Expression of the cloned protein [designated the vasopressin-activated, calcium-mobilizing (VACM-1) protein] in COS-1 cells, resulted in increased 125I-labeled AVP binding [dissociation constant (Kd) of approximately 2 nM] and increased AVP-induced mobilization of Ca2+. Importantly, 125I-AVP could be immunoprecipitated both from detergent-solubilized membranes from COS-1 cells expressing VACM-1 protein and from an in vitro translation system, in which VACM-1 protein was synthesized, using antibodies prepared against a synthetic peptide derived from the NH2-terminal sequence of VACM-1. Interestingly, immunohistochemical staining of rabbit kidney sections with this antibody showed specific staining of collecting tubule epithelia. The deduced amino acid sequence is not homologous with any nucleic acid or amino acid sequences reported to date, including those of the V1 and V2 AVP receptors. The VACM-1 protein may represent a novel AVP receptor.
 ...
PMID:Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla. 761 60

We have localized the human homolog of the rabbit vasopressin-activated calcium-mobilizing receptor VACM-1 to a region close to the gene for ataxia telangiectasia ATM on chromosome 11q22-23. We have determined the complete amino acid sequence of the human Hs-VACM-1 protein, which is 780 amino acids long. The human and rabbit sequences are highly conserved, differing at only seven amino acids. Northern analysis of the human gene showed expression in a wide range of human tissues. The Hs-VACM-1 gene has homology with the Caenorhabditis elegans gene Ce-cul-5, a member of a family of cullin genes that are involved in cell cycle regulation and that might, when mutated, contribute to tumor progression.
 ...
PMID:Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23. 903 4

Vasopressin is one of several small neuropeptides that are reported to be autocrine growth factors for small cell carcinoma of the lung (SCCL). It has been assumed that this peptide exercises its mitogenic influences through the vasopressin V1a receptor, and we have previously demonstrated that this receptor is expressed by classical and variant SCCL. Activation of the vasopressin V1a receptor produces changes in phospholipases C, D, and A2, in protein kinase C, and in Ca2+ mobilization. This study demonstrates that SCCL cells express not only vasopressin V1a receptors but also mRNAs and proteins representing normal V1b receptors and V2 receptors. They were also shown to express mRNA for a human form of the putative receptor rabbit vasopressin-activated calcium-mobilizing receptor (VACM-1). Additionally, SCCL tumor cells were found to express mRNA and protein representing a possible nonfunctional, shortened, "diabetic" form of the vasopressin V2 receptor that is the product of incomplete posttranscriptional splicing. At least four of these five vasopressin receptors were produced by cell lines exemplifying classical and variant forms of SCCL. No differences in the sequences for the V1 receptors between classical and variant SCCL were found. However, although the nature and expression of both vasopressin V1 receptors and human VACM are apparently unaffected by dedifferentiation in SCCL, only the abnormal (and probably nonfunctional) form of the V2 receptor could be demonstrated in variant cell line NCI H82. Functional engagement of vasopressin V2 receptors is reported to produce rises in cAMP and activation of protein kinase A, whereas stimulation of V1b receptors is believed to produce similar changes to those produced by V1a receptors, i.e., activation of phospholipases and of protein kinase C. Stimulation of VACM receptors raises intracellular free Ca2+ through currently unknown but phosphoinositide-independent mechanisms. The presence of all known vasopressin receptors that are, together, potentially capable of inducing several different transduction cascades in small cell tumor cells suggests that this peptide serves a multifaceted role in tumor physiology.
 ...
PMID:Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide. 958 26

The vasopressin-activated calcium-mobilizing (VACM-1) protein is a novel arginine vasopressin (AVP) receptor that shares sequence homology with a cullin multigene family but not with the AVP receptors. To characterize the VACM-1 receptor, we examined its tissue-specific expression using Northern blot, RT-PCR, and immunostaining analyses. Northern blot hybridization identified a 6. 4-kb cRNA species that was expressed in the rabbit kidney medulla, brain, heart, and ovaries. In human tissue, VACM-1 mRNA is a larger (7.5 kb) cRNA found in the kidney, brain, heart, placenta, and skeletal muscle. VACM-1-specific RT-PCR products were detected in mRNA from rabbit kidney medulla, brain, heart, and mesenteric arteries. No expression of VACM-1 could be detected in rabbit aorta, gastrointestinal tract, or liver. Coimmunostaining with anti-VACM-1 antibodies (Ab) and a specific vascular endothelial cell marker, CD31 monoclonal Ab, localized VACM-1 expression to the vasculature in specific tissues. We identified the kidney cells expressing VACM-1 receptor by coimmunostaining with the following monoclonal Ab, which recognize epitopes in specific segments of the nephron: rct-30 Ab, reactive against the cortical and medullary collecting tubule (CT) cells; mr-omct Ab, reactive against the mitochondria-rich cells of the outer medullary CT; and an Ab specific against the loop of Henle segment. These studies indicated that the VACM-1 receptor is expressed only in the medullary CT. Kidney coimmunostaining with anti-VACM-1 and CD31 Ab identified VACM-1-receptor expression in glomeruli and medullary vascular bundles. These results demonstrate that the novel VACM-1 receptor, expressed in many organs, is localized to the endothelial cells. In the kidney, it is also expressed in the medullary CT cells. Thus VACM-1 may be involved in the regulation of endothelial permeability and water transport in the CT.
 ...
PMID:VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule. 995 Sep 50

The distributions of two newly discovered receptors, the vasopressin-activated calcium-mobilizing receptor (VACM-1) and the dual angiotensin II/vasopressin receptor (AII/AVP), in the central nervous system (CNS) of the rat were determined using reverse transcriptase-polymerase chain reaction and in situ hybridization. The sequence of the rat VACM-1 cDNA was determined and found very homologous to the rabbit and human sequences. Both VACM-1 and AII/AVP receptor genes were widely expressed in the brain, but differed according to the cell type studied. Glial cells were very faintly labelled. The epithelial cells of the choroid plexuses, the ependymal cells and the pia mater were all labelled. Both genes were most active in neurones throughout the CNS. VACM-1 and AII/AVP receptors were detected in neurones previously shown to possess V1a and V1b vasopressin receptors, and/or the AT1 and AT2 angiotensin II receptors in many brain areas. This was the case for the magnocellular neurones of the supraoptic and paraventricular nuclei of the hypothalamus. We suggest that the VACM-1 and AII/AVP receptors may account for the V2-like responses to vasopressin by these neurones which lack a genuine V2 vasopressin receptor.
 ...
PMID:Expression of the genes encoding the vasopressin-activated calcium-mobilizing receptor and the dual angiotensin II/vasopressin receptor in the rat central nervous system. 1084 13

The vasopressin-activated calcium-mobilizing (VACM-1) protein is a unique arginine vasopressin (AVP) receptor which shares sequence homology with the cullins, genes involved in the regulation of cell cycle transitions. Unlike either cullins or AVP receptors, however, VACM-1 is expressed exclusively in the vascular endothelial cells and in the renal collecting tubule cells. In order to test the hypothesis that the expression of VACM-1 might be correlated with the cell cycle, and to establish an endothelial cell model for the VACM-1 receptor, we examined VACM-1 expression in rat adrenal medulla endothelial cells (RAMEC). Northern and Western blot analyses of mRNA and protein from RAMEC identified presence of 6.4 kb mRNA and a Mr 81 kDa protein, respectively. Immunostaining of RAMEC with anti-VACM-1 antibodies and Western blot analyses indicated that in RAMEC, VACM-1 protein expression is dependent on the cell cycle. VACM-1 protein virtually disappears during the S phase and localizes to the cytosol during cell division and to the cell membrane at the completion of cytokinesis. Furthermore, pretreatment of RAMEC with anti-VACM-1 specific antibodies increased basal levels of Ca2+and attenuated the AVP-dependent increase in cytosolic Ca2+. In summary, these results indicate that VACM-1 protein expression in RAMEC membrane is linked to the cell cycle, and consequently, VACM-1 may be involved in the regulation of cell division.
 ...
PMID:Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle. 1140 51

Vasopressin-activated Ca2+-mobilizing (VACM)-1 gene product is a 780-amino acid membrane protein that shares sequence homology with cullins, a family of genes involved in the regulation of cell cycle. However, when expressed in vitro, VACM-1 attenuates basal and vasopressin- and forskolin-induced cAMP production. Mutating the PKA-dependent phosphorylation site in the VACM-1 sequence (S730AVACM-1) prevents this inhibitory effect. To further examine the biological role of VACM-1, we studied the effect of VACM-1 and S730AVACM-1 proteins on cellular proliferation and gene expression in Chinese hamster ovary and COS-1 cells. Cellular proliferation of VACM-1-expressing cell lines was significantly lower compared with that of the vector-transfected cells, whereas it was significantly increased in S730AVACM-1-derived cell lines. Furthermore, expression of VACM-1 but not S730AVACM-1 protein retarded cytokinesis and prevented MAPK phosphorylation. Screening with the Human PathwayFinder-1 GEArray system and subsequent Western blot analysis demonstrated that VACM-1 induces p53 mRNA and protein expression. In summary, VACM-1 inhibits cellular growth by a mechanism that involves cAMP, MAPK phosphorylation, and p53 expression.
 ...
PMID:VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways. 1291 6

We have sequenced a 4.9kb clone (KLB22) which shares 99% sequence homology with the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5' terminus sequence of KLB22 cDNA (nucleotides 1-1961) is continuous and overlapping with nucleotides 1226-3186 of the VACM-1 cDNA sequence. The 3'UTR of KLB22 cDNA extends beyond the 3'UTR of VACM-1 by 2999nt. KLB22 cDNA encodes a 497 amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM-1 protein. The in vitro translation of KLB22 cDNA yields a 59kDa protein. When expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus. KLB22 cDNA transfected cells show increased growth rates and increased levels of phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be detected in kidney and in heart atrium. These results suggest that truncated VACM-1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.
 ...
PMID:Truncated form of VACM-1/cul-5 with an extended 3' untranslated region stimulates cell growth via a MAPK-dependent pathway. 1658 Oct 22

The E3 ubiquitin (Ub)-protein ligases (E3s) play a role as regulators of protein trafficking and degradation. We aimed to integrate the profile of E3s in rat kidney and examine the changes in protein abundance of the selected E3s in response to 1-deamino-8-D-arginine vasopressin (dDAVP) stimulation/withdrawal. Sprague-Dawley rats were infused with vehicle (n = 13), dDAVP for 5 days (n = 13), or dDAVP was withdrawn for periods (15 min, 30 min, 1, 3, 6, 12, or 24 h) after 5-day infusion (n = 46). Total RNA was isolated from the inner medulla (IM) for transcriptome analysis. Plasma membrane (PM)- or intracellular vesicle (ICV)-enriched fractions of whole kidney were immunoisolated for liquid chromatography-tandem mass spectrometry analysis. dDAVP infusion for 5 days (D5d) significantly increased urine osmolality, which was maintained during 3-h withdrawal of dDAVP after 5-day infusion (D5d-3h). Consistent with this, aquaporin-2 (AQP2) expression in the PM fractions of D5d and D5d-3h increased, whereas AQP2 expression in the ICV fractions of D5d-3h was further increased, indicating internalization of AQP2. Transcriptome analysis revealed 86 genes of E3s and LC-MS/MS analysis demonstrated 16 proteins of E3s. Among these, seven E3s (BRCA1, UBR4, BRE1B, UHRF1, NEDD4, CUL5, and FBX6) were shared. RT-PCR demonstrated mRNA expressions of the seven identified E3s in the kidney, and immunoblotting demonstrated changes in protein abundance of the selected E3s (BRE1B, NEDD4, and CUL5) in response to dDAVP stimulation/withdrawal or lithium-induced nephrogenic diabetes insipidus. The rate of AQP2 degradation was retarded in mpkCCDc14 cells with small interfering RNA-mediated knockdown of NEDD4 or CUL5. Taken together, identified E3s could be involved in the degradation of proteins associated with vasopressin-induced urine concentration.
 ...
PMID:E3 ubiquitin-protein ligases in rat kidney collecting duct: response to vasopressin stimulation and withdrawal. 2173 99