Interaction of NO-sensitive guanylyl cyclase with Src-like kinases
- Poster presentation NO-sensitive guanylyl cyclases (soluble guanylyl cyclase, sGC) are among the key regulators of intracellular cGMP concentration. The mechanisms underlying NO-mediated activation of sGC are quite well understood, however, little is known about the fine-tuning of sGC activity through alternative mechanisms such as protein phosphorylation. Several reports have demonstrated the reversible phosphorylation of sGC on serine/threonine residues, and it has been speculated, though not experimentally proven, that sGC might also be phosphorylated on tyrosine residues. Using broad-spectrum phosphatase inhibitors we were able to demonstrate tyrosine phosphorylation at Tyr192 of the beta 1 subunit of human sGC in COS1 cells. This residue forms part of a sequence segment (YEDL) representing a preferential binding site for SH2 domains of Src-like kinases. Pull-down assays and co-immunoprecipitation experiments showed that Src can indeed bind via its SH2 domain to pTyr192 of beta 1 indicating that tyrosine phosphorylation of sGC may be followed by recruitment of Src-like kinases to the phosphorylated beta 1 subunit. In support of this hypothesis, immunofluorescence studies showed a colocalization of overexpressed sGC and Src at the plasma membrane of COS1 and Hela cells. Together, our results point to an unexpected crosstalk between tyrosine kinase pathway(s) and the NO/cGMP signalling cascade which may result in translocation of the predominantly cytosolic sGC to the cytosolic face of the plasma membrane.
Author: | Sylke PiochGND, Sabine MeurerGND, Steffen GroßGND, Werner Müller-EsterlORCiDGND |
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URN: | urn:nbn:de:hebis:30-58696 |
DOI: | https://doi.org/10.1186/1471-2210-5-S1-P43 |
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):P43 |
Page Number: | 1 |
First Page: | 1 |
Last Page: | 1 |
Note: | © BioMed Central Ltd 2005 |
Source: | BMC Pharmacology 2005, 5(Suppl 1):P43 ; doi:10.1186/1471-2210-5-S1-P43 ; from 2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications, Potsdam, Germany. 10–12 June, 2005 |
HeBIS-PPN: | 216705304 |
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): | Deutsches Urheberrecht |