| Autor: |
Shi, Chong-Shan, Lee, Sang Bong, Sinnarajah, Srikumar, Dessauer, Carmen W., Rhee, Sue Goo, Kehrl, John H. |
| Zdroj: |
Journal of Biological Chemistry; June 2001, Vol. 276 Issue: 26 p24293-24300, 8p |
| Abstrakt: |
Regulator of G-protein signaling 3 (RGS3) enhances the intrinsic rate at which Gαiand Gαqhydrolyze GTP to GDP, thereby limiting the duration in which GTP-Gαiand GTP-Gαqcan activate effectors. Since GDP-Gα subunits rapidly combine with free Gβγ subunits to reform inactive heterotrimeric G-proteins, RGS3 and other RGS proteins may also reduce the amount of Gβγ subunits available for effector interactions. Although RGS6, RGS7, and RGS11 bind Gβ5in the absence of a Gγ subunit, RGS proteins are not known to directly influence Gβγ signaling. Here we show that RGS3 binds Gβ1γ2subunits and limits their ability to trigger the production of inositol phosphates and the activation of Akt and mitogen-activated protein kinase. Co-expression of RGS3 with Gβ1γ2inhibits Gβ1γ2-induced inositol phosphate production and Akt activation in COS-7 cells and mitogen-activated protein kinase activation in HEK 293 cells. The inhibition of Gβ1γ2signaling does not require an intact RGS domain but depends upon two regions in RGS3 located between acids 313 and 390 and between 391 and 458. Several other RGS proteins do not affect Gβ1γ2signaling in these assays. Consistent with the in vivoresults, RGS3 inhibits Gβγ-mediated activation of phospholipase Cβ in vitro. Thus, RGS3 may limit Gβγ signaling not only by virtue of its GTPase-activating protein activity for Gα subunits, but also by directly interfering with the activation of effectors. |
| Databáze: |
Supplemental Index |
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