Related Experiment Video

Updated: Aug 12, 2026

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound
08:51

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound

Published on: May 8, 2012

Integrin-mediated signal transduction in cells lacking focal adhesion kinase p125FAK

K Ueki1, T Mimura, T Nakamoto

  • 1Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.

FEBS Letters
|August 28, 1998
PubMed

Insights

In FAK-deficient cells, the Src homology 3 (SH3) domain of p130Cas is crucial for phosphorylation. Cell adhesion kinase beta (CAKbeta) compensates for FAK, mediating integrin signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Integrin-mediated signaling regulates cell adhesion and migration.
  • p130Cas (Cas) is a key substrate in integrin signaling pathways.
  • Focal adhesion kinase p125FAK (FAK) is a critical mediator of Cas phosphorylation.

Purpose of the Study:

  • To investigate the mechanism of integrin-dependent p130Cas phosphorylation in FAK-deficient cells.
  • To identify potential FAK substitutes in mediating Cas phosphorylation.

Main Methods:

  • Analysis of FAK-deficient mouse fibroblast cell lines.
  • Transient expression of Cas mutant proteins.
  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to detect tyrosine phosphorylation.

Main Results:

  • The Src homology 3 (SH3) domain of Cas is essential for adhesion-mediated phosphorylation in FAK-/- cells.
  • Cell adhesion kinase beta (CAKbeta), a FAK subfamily kinase, is expressed in FAK-/- cells.
  • CAKbeta associates with Cas in a Cas-SH3-dependent manner.
  • Integrin stimulation induces tyrosine phosphorylation of CAKbeta in FAK-/- cells.

Conclusions:

  • CAKbeta can substitute for FAK in mediating integrin-dependent p130Cas phosphorylation in FAK-deficient cells.
  • CAKbeta plays a role in integrin-mediated signal transduction in the absence of FAK.

More Related Videos

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes09:14

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

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 the...
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...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
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...
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...