Characterization of MRIP2 as a NO-sensitive guanylyl cyclase-associated protein

  • Poster presentation: NO-sensitive guanylyl cyclases (sGCs) are cytosolic receptors for nitric oxide (NO) catalyzing the conversion of GTP to cGMP. sGCs are obligate heterodimers composed of one alpha and beta subunit each. The allosteric mechanism of sGC activation via NO is well understood, however, our knowledge about alternative mechanisms such as protein-protein interactions regulating activity, availability, translocation and expression of sGC is rather limited. In a search by the yeast two-hybrid system using the catalytic domain of the alpha1 subunit as the bait, we have identified two structurally related proteins AGAP1 [1] and MRIP2 as novel sGC interacting proteins. MRIP2 is a multi-domain protein of 75 kDa comprising a single PH and ArfGAP domain each and two ankyrin repeats. Co-immunoprecipitation experiments using COS1 cells overexpressing both proteins demonstrated the interaction of MRIP2 with both subunits of the sGC alpha1beta1. Confocal microscopical analysis showed a prominent plasma membrane staining of MRIP2. This membrane association is mediated through an N-terminal myristoylation site and through binding of its PH domain to phospholipids such as phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2). We hypothesize that MRIP2 may represent an acceptor protein for sGC that mediates recruitment of cytosolic sGC to the plasma membrane or other subcellular compartments.

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Author:Simone Matt, Sabine MeurerGND, Steffen GroßGND, Werner Müller-EsterlORCiDGND
URN:urn:nbn:de:hebis:30-70762
DOI:https://doi.org/10.1186/1471-2210-5-S1-P37
ISSN:1471-2210
Parent Title (English):BMC pharmacology
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2009/09/20
Year of first Publication:2005
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications, Potsdam, Germany. 10–12 June, 2005
Release Date:2009/09/20
Volume:5
Issue:(Suppl 1):P37
Page Number:1
First Page:1
Last Page:1
Note:
© BioMed Central Ltd 2005
Source:BMC Pharmacology 2005, 5(Suppl 1):P37 ; doi:10.1186/1471-2210-5-S1-P37 ; from 2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications, Potsdam, Germany. 10–12 June, 2005
HeBIS-PPN:21896899X
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoDeutsches Urheberrecht