PLCββ1-SHP-2 complex,PLCββ1 tyrosine dephosphorylation and SHP-2 phosphatase activity: A new part of Angiotensin II signaling?

Background: 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. results: 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. conclusions: 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. © 2011 cal et al; licensee biomed central ltd.