Related Experiment Video

Updated: Mar 28, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

3.9K

PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling

Suowen Xu1, Chang Hoon Ha1, Weiye Wang1

  • 1Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.

Cellular Signalling
|December 27, 2015
PubMed

Insights

Platelet endothelial cell adhesion molecule-1 (PECAM1) specifically mediates flow-induced Gab1 and endothelial nitric oxide synthase (eNOS) activation in endothelial cells. This pathway is crucial for the protective effects of laminar blood flow on cardiovascular health.

Area of Science:

  • Cardiovascular Biology
  • Endothelial Cell Signaling
  • Mechanotransduction

Background:

  • Endothelial dysfunction contributes to cardiovascular diseases like hypertension and atherosclerosis.
  • Laminar blood flow influences endothelial cell (EC) function via signaling pathways.
  • Previous work linked flow-stimulated Gab1 phosphorylation to eNOS activation and atheroprotection.

Purpose of the Study:

  • To elucidate the molecular mechanisms of flow-induced Gab1 tyrosine phosphorylation and downstream signaling.
  • To determine the specific role of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM1) in this process.

Main Methods:

  • Utilized small interfering RNA (siRNA) to target PECAM1 and SHP2.
  • Employed pharmacological inhibition of PI3K.
  • Investigated flow and Hepatocyte Growth Factor (HGF) stimulation in endothelial cells.
  • Assessed Gab1 and eNOS activation, phosphorylation, and membrane translocation.
  • Examined flow-induced signaling in PECAM1 knockout mice.

Main Results:

  • PECAM1 specifically mediated flow-induced Gab1 tyrosine phosphorylation, Akt, and eNOS activation, unlike HGF.
  • siRNA targeting PECAM1 abolished flow-induced signaling but not HGF-induced signaling.
  • SHP2 phosphatase was involved in both flow and HGF signaling pathways.
  • PI3K inhibition affected flow-mediated signaling.
  • PECAM1 knockout mice showed reduced in vivo flow-induced Gab1 and eNOS phosphorylation.

Conclusions:

  • PECAM1 is a key mechanosensor that specifically links laminar blood flow to Gab1 and eNOS activation in endothelial cells.
  • This PECAM1-dependent pathway is critical for the atheroprotective effects of laminar flow.
  • Findings reveal a novel signaling mechanism in endothelial mechanotransduction.

Keywords:
Gab1Laminar flowPECAM1

More Related Videos

Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart06:51

Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart

Published on: August 10, 2018

8.9K
Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum09:40

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

18.5K

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.2K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.8K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
6.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.9K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
12.4K