PLCβ1-SHP-2 complex, PLCβ1 tyrosine dephosphorylation and SHP-2 phosphatase activity: a new part of Angiotensin II signaling?

• Main Authors: Rossi Gian, Dal Maso Lucia, Pagnin Elisa, Davis Paul A, Bordin Luciana, Calò Lorenzo A, Pessina Achille C, Clari Giulio
• Format: Article
• Language: English
• Published: BMC 2011-06-01
• Series: Journal of Biomedical Science
• Subjects: Angiotensin II signaling; SHP-2; PLCβ1; SHP-2-PLCβ1 complex
• Online Access: http://www.jbiomedsci.com/content/18/1/38
• ISSN: 1021-7770; 1423-0127

<p>Abstract</p> <p>Background</p> <p>Angiotensin II (Ang II) signaling occurs via two major receptors which activate non-receptor tyrosin kinases that then interact with protein tyrosin-phosphatases (PTPs) to regulate cell function. SHP-2 is one such important PTP that also functions as an adaptor to promote downstream signaling pathway. Its role in Ang II signaling remains to be clarified.</p> <p>Results</p> <p>Using cultured normal human fibroblasts, immunoprecipitation and western blots, we show for the first time that SHP-2 and PLCβ1 are present as a preformed complex. Complex PLCβ1 is tyr-phosphorylated basally and Ang II increased SHP-2-PLCβ1 complexes and caused complex associated PLCβ1 tyr-phosphorylation to decline while complex associated SHP-2's tyr-phosphorylation increased and did so via the Ang II type 1 receptors as shown by Ang II type 1 receptor blocker losartan's effects. Moreover, Ang II induced both increased complex phosphatase activity and decreased complex associated PLCβ1 tyr-phosphorylation, the latter response required regulator of G protein signaling (RGS)-2.</p> <p>Conclusions</p> <p>Ang II signals are shown for the first time to involve a preformed SHP-2-PLCβ1 complex. Changes in the complex's PLCβ1 tyr-phosphorylation and SHP-2's tyr-phosphorylation as well as SHP-2-PLCβ1 complex formation are the result of Ang II type 1 receptor activation with changes in complex associated PLCβ1 tyr-phosphorylation requiring RGS-2. These findings might significantly expand the number and complexity of Ang II signaling pathways. Further studies are needed to delineate the role/s of this complex in the Ang II signaling system.</p>