Unknown

Dataset Information

0

GIT1 mediates HDAC5 activation by angiotensin II in vascular smooth muscle cells.


ABSTRACT: The G protein-coupled receptor (GPCR)-kinase2 interacting protein1 (GIT1) is a scaffold protein involved in angiotensin II (Ang II) signaling. Histone deacetylase-5 (HDAC5) has emerged as an important substrate of calcium/calmodulin-dependent protein kinase II (CamK II) in GPCR signaling. Here we investigated the hypothesis that Ang II-mediated vascular smooth muscle cell (VSMC) gene transcription involves GIT1-CamK II-dependent phosphorylation of HDAC5.Ang II rapidly stimulated phosphorylation of HDAC5 at Ser498 in VSMCs. Knockdown of GIT1 significantly decreased HDAC5 phosphorylation induced by Ang II. The involvement of Src, phospholipase gamma (PLCgamma), and CamK II in GIT1-mediated HDAC5 phosphorylation was demonstrated. The association of GIT1 and CamK II was constitutive but increased after stimulation with Ang II. Moreover, the interaction of GIT1 and CamK II through the ARF GTPase-activating protein (ARF-GAP) and coiled-coil domains of GIT1 was essential for the phosphorylation of HDAC5. Finally, knockdown of GIT1 decreased myocyte enhancer factor 2 transcriptional activity induced by Ang II.This study identifies a novel function for GIT1 as a mediator of Ang II-induced VSMC gene transcription via a Src-PLCgamma-CamK II-HDAC5 signaling pathway.

SUBMITTER: Pang J 

PROVIDER: S-EPMC2735338 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

GIT1 mediates HDAC5 activation by angiotensin II in vascular smooth muscle cells.

Pang Jinjiang J   Yan Chen C   Natarajan Kanchana K   Cavet Megan E ME   Massett Michael P MP   Yin Guoyong G   Berk Bradford C BC  

Arteriosclerosis, thrombosis, and vascular biology 20080221 5


<h4>Objective</h4>The G protein-coupled receptor (GPCR)-kinase2 interacting protein1 (GIT1) is a scaffold protein involved in angiotensin II (Ang II) signaling. Histone deacetylase-5 (HDAC5) has emerged as an important substrate of calcium/calmodulin-dependent protein kinase II (CamK II) in GPCR signaling. Here we investigated the hypothesis that Ang II-mediated vascular smooth muscle cell (VSMC) gene transcription involves GIT1-CamK II-dependent phosphorylation of HDAC5.<h4>Methods and results<  ...[more]

Similar Datasets

| S-EPMC2373882 | biostudies-literature
| S-EPMC4201143 | biostudies-literature
| S-EPMC6528929 | biostudies-literature
| S-EPMC2963313 | biostudies-literature
| S-EPMC6038660 | biostudies-literature
| S-EPMC1850970 | biostudies-literature
| S-EPMC3641899 | biostudies-literature
| S-EPMC3204383 | biostudies-literature
| S-EPMC2642522 | biostudies-literature
| S-EPMC3058730 | biostudies-literature