| Abnormal bradykinin signalling in fibroblasts deficient in the PIP(2) 5-phosphatase, ocrl1. | |
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MedLine Citation:
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PMID: 19172411 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The oculocerebrorenal syndrome of Lowe (Lowe syndrome) is an X-linked disorder of phosphatidylinositol metabolism characterized by congenital cataracts, renal proximal tubulopathy and neurological deficits. The disorder is due to the deficiency of the phosphatidylinositol 4,5-bisphosphate (PIP(2)) 5-phosphatase, ocrl1. PIP(2) is critical for numerous cellular processes, including cell signalling, actin reorganization and protein trafficking, and is chronically elevated in patients with Lowe syndrome. The elevation of PIP(2) cells of patients with Lowe syndrome provides the unique opportunity to investigate the roles of this phospholipid in fundamental cellular processes. We previously demonstrated that ocrl1 deficiency causes alterations in the actin cytoskeleton. Since actin remodelling is strongly activated by [Ca(+2)], which increases in response to IP(3) production, we hypothesized that altered calcium signalling might contribute to the observed abnormalities in actin organization. Here we report a specific increase in bradykinin-induced Ca(+2) mobilization in Lowe fibroblasts. We show that the abnormal bradykinin signalling occurs in spite of normal total cellular receptor content. These data point to a novel role for ocrl1 in agonist-induced calcium release. |
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Authors:
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S F Suchy; J C Cronin; R L Nussbaum |
Publication Detail:
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Type: Journal Article Date: 2009-01-28 |
Journal Detail:
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Title: Journal of inherited metabolic disease Volume: 32 ISSN: 1573-2665 ISO Abbreviation: J. Inherit. Metab. Dis. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-02 Completed Date: 2009-07-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7910918 Medline TA: J Inherit Metab Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 280-8 Citation Subset: IM |
Affiliation:
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Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. sharon@genedx.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Bradykinin / pharmacology* Calcimycin / pharmacology Calcium / metabolism Calcium Signaling / genetics, physiology* Cell Line Fibroblasts / drug effects, enzymology, physiology* Histamine / pharmacology Humans Inositol 1,4,5-Trisphosphate Receptors / drug effects Ionophores / pharmacology Phosphoric Monoester Hydrolases / genetics, physiology* Platelet-Derived Growth Factor / pharmacology Receptors, Bradykinin / drug effects Tubulin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Inositol 1,4,5-Trisphosphate Receptors; 0/Ionophores; 0/Platelet-Derived Growth Factor; 0/Receptors, Bradykinin; 0/Tubulin; 51-45-6/Histamine; 52665-69-7/Calcimycin; 58-82-2/Bradykinin; 7440-70-2/Calcium; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.36/OCRL protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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