- 作者: Lorenzo A Calo; Luciana Bordin; Paul A Davis; Elisa Pagnin; Lucia Dal Maso; Gian Paolo Rossi; Achille C Pessina; Giulio Clari
- 作者服務機構: Department of Clinical and Experimental Medicine, Clinica Medica 4 University of Padova, School of Medicine, Italy
- 中文摘要: --
- 英文摘要:
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 tyrphosphorylation
as well as SHP-2-PLCβ1 complex formation are the result of Ang II
type 1 receptor activation with changes in complex associated PLCβ1 tyrphosphorylation
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. - 中文關鍵字: --
- 英文關鍵字: Angiotensin II signaling; SHP-2; PLCβ1; SHP-2-PLCβ1 complex