Related Experiment Video

Updated: Jul 22, 2026

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring
06:11

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Published on: May 21, 2017

Role of Raf in vascular protection from distinct apoptotic stimuli

Alireza Alavi1, John D Hood, Ricardo Frausto

  • 1Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)
|July 5, 2003
PubMed

Insights

Basic fibroblast growth factor and vascular endothelial growth factor differentially regulate endothelial cell survival by activating Raf-1 through distinct pathways, impacting apoptosis during angiogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Angiogenesis Research

Background:

  • Raf kinases are implicated in endothelial cell survival.
  • Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are key regulators of angiogenesis.

Purpose of the Study:

  • To investigate the differential activation of Raf-1 by bFGF and VEGF.
  • To elucidate the distinct pathways through which these growth factors promote endothelial cell survival and inhibit apoptosis.

Main Methods:

  • Investigated Raf-1 activation by bFGF and VEGF in human endothelial cells and chick embryo vasculature.
  • Utilized techniques to analyze protein phosphorylation (e.g., PAK-1, Src kinase) and subcellular localization (mitochondrial translocation).
  • Assessed the role of mitogen-activated protein kinase kinase-1 (MEK1) in mediating protective effects.

Main Results:

  • bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation, leading to mitochondrial translocation and protection from intrinsic apoptosis, independent of MEK1.
  • VEGF activated Raf-1 via Src kinase, causing tyrosine phosphorylation and MEK1-dependent protection from extrinsic apoptosis.
  • Demonstrated distinct mechanisms of Raf-1 activation by bFGF and VEGF.

Conclusions:

  • Raf-1 acts as a crucial regulator of endothelial cell survival during angiogenesis.
  • Differential activation of Raf-1 by growth factors mediates protection against specific apoptotic pathways.
  • Understanding these pathways is vital for therapeutic strategies targeting angiogenesis.

More Related Videos

Modified Langendorff Perfusion for Extended Perfusion Times of Rodent Cardiac Grafts06:22

Modified Langendorff Perfusion for Extended Perfusion Times of Rodent Cardiac Grafts

Published on: June 14, 2024

Simple and Effective Procedure for Hemostasis in Mouse Arteries05:34

Simple and Effective Procedure for Hemostasis in Mouse Arteries

Published on: November 28, 2025

Related Concept Videos

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...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
Vascular Spasm01:16

Vascular Spasm

The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...
Autoregulation of Blood Flow01:17

Autoregulation of Blood Flow

Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.