Related Experiment Video

Updated: Aug 6, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

p38 MAPK activation coupled to endocytosis is a determinant of endothelial monolayer integrity

Shahid S Siddiqui1, Zeba K Siddiqui, Shahab Uddin

  • 1Department of Pharmacology, University of Illinois College of Medicine, 835 South Wolcott Ave. (M/C 868), Chicago, IL 60612, USA. ssiddiqu@uic.edu

American Journal of Physiology. Lung Cellular and Molecular Physiology
|August 8, 2006
PubMed

Insights

Endocytosis regulates endothelial cell function by activating mitogen-activated protein kinase (MAPK). Caveolae-mediated endocytosis and p38 MAPK signaling promote endothelial monolayer integrity through cell proliferation and survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endothelial Cell Biology

Background:

  • Endothelial monolayer integrity is crucial for vascular function.
  • Mitogen-activated protein kinase (MAPK) pathways play roles in cell signaling.
  • Endocytosis is a key cellular process for internalizing molecules.

Purpose of the Study:

  • To investigate the role of endocytosis in regulating MAPK activation in rat lung microvessel endothelial cells (RLMVEC).
  • To determine the impact of p38 MAPK activation on endothelial monolayer integrity.
  • To explore the interaction between caveolin-1 and p38 MAPK in endothelial cells.

Main Methods:

  • Cultured RLMVEC in serum-free medium.
  • Induced MAPK phosphorylation with albumin supplementation.
  • Utilized coimmunoprecipitation and immunofluorescence staining to assess protein interactions.
  • Employing small interfering RNA (siRNA) to knockdown caveolin-1 expression.

Main Results:

  • Albumin induced p38 MAPK phosphorylation in RLMVEC.
  • Endocytosis engagement regulated p38 MAPK activation, promoting cell proliferation and reducing apoptosis.
  • Caveolin-1 interacted with p38 MAPK.
  • Caveolin-1 knockdown reduced endocytosis and p38 MAPK activation, impairing monolayer formation.

Conclusions:

  • Caveolae-mediated endocytosis activates p38 MAPK signaling.
  • This signaling pathway is vital for maintaining endothelial monolayer integrity by promoting cell proliferation and survival.

More Related Videos

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation12:55

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation

Published on: December 9, 2021

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption09:20

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption

Published on: October 4, 2019

Related Concept Videos

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 produces two-second...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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 hydroxylase and factor...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...