Related Experiment Video

Updated: Jul 7, 2026

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
13:45

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin

Published on: December 23, 2010

Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins

Eun Young Choi1, Valeria V Orlova, Susanna C Fagerholm

  • 1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Blood
|February 2, 2008
PubMed

Insights

Cbl-b deficiency enhances immune cell adhesion and migration by activating leukocyte function-associated antigen-1 (LFA-1) through increased interaction with 14-3-3 proteins. This pathway is crucial for inflammatory responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Leukocyte function-associated antigen-1 (LFA-1) is a key immune cell adhesion molecule regulated by intracellular signaling.
  • 14-3-3 proteins are known regulators of LFA-1 activity.
  • Cbl-b is an adapter molecule and ubiquitin ligase involved in various signaling pathways.

Purpose of the Study:

  • To identify a novel regulatory pathway for LFA-1 activity involving Cbl-b.
  • To investigate the role of Cbl-b in immune cell adhesion and migration.
  • To elucidate the molecular mechanism by which Cbl-b deficiency affects LFA-1 function.

Main Methods:

  • Utilized Cbl-b knockout (Cbl-b-/-) mice and bone marrow chimeras.
  • Assessed macrophage recruitment in vivo using thioglycollate-induced peritonitis.
  • Performed in vitro adhesion assays of bone marrow-derived mononuclear phagocytes (BMDMs) to endothelial cells and ICAM-1.
  • Analyzed LFA-1 phosphorylation and its interaction with 14-3-3 proteins.

Main Results:

  • Cbl-b-/- mice exhibited increased macrophage recruitment and enhanced BMDM adhesion to endothelial cells.
  • LFA-1 activation was responsible for the increased adhesion and recruitment observed in Cbl-b deficient cells.
  • Cbl-b deficiency led to increased LFA-1 beta2-chain phosphorylation, enhancing 14-3-3beta binding and LFA-1 activation.
  • Disruption of the 14-3-3/LFA-1 interaction abolished the enhanced adhesion in Cbl-b-/- BMDMs.

Conclusions:

  • Cbl-b deficiency activates LFA-1, leading to enhanced inflammatory cell recruitment.
  • The mechanism involves increased phosphorylation of the LFA-1 beta2-chain, promoting 14-3-3 protein association.
  • This study reveals a new Cbl-b-dependent pathway regulating LFA-1 and immune cell trafficking.

More Related Videos

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response12:50

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

Published on: September 15, 2017

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Acute Inflammation II: Cellular Phase01:26

Acute Inflammation II: Cellular Phase

The cellular phase of acute inflammation is a tightly orchestrated sequence of events that recruits leukocytes, primarily neutrophils, to sites of tissue injury or infection. Following the initial vascular changes, this phase ensures effective immune cell migration, activation, and function at the affected site to eliminate pathogens and initiate tissue repair.Leukocyte Recruitment CascadeLeukocyte recruitment happens in four steps: margination, adhesion, transmigration, and chemotaxis. Reduced...
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...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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...