TY  - JOUR
A1  - Pioch, Sylke
A1  - Meurer, Sabine
A1  - Groß, Steffen
A1  - Müller-Esterl, Werner
T1  - Interaction of NO-sensitive guanylyl cyclase with Src-like kinases
T2  - BMC pharmacology
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7064
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-58696
SN  - 1471-2210
N1  - © BioMed Central Ltd 2005
VL  - 5
IS  - (Suppl 1):P43
SP  - 1
EP  - 1
PB  - BioMed Central
CY  - London
ER  -