Related Experiment Video

Updated: Aug 19, 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-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion

Denis Tvorogov1, Xue-Jie Wang, Roy Zent

  • 1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Journal of Cell Science
|January 20, 2005
PubMed

Insights

Phospholipase C-gamma1 (PLC-gamma1) is crucial for efficient cell adhesion to fibronectin, with its Src kinase-dependent phosphorylation at Tyr783 being essential for this process.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Integrin engagement triggers signaling pathways like focal-adhesion kinase (FAK) and Src kinase activation.
  • The specific role of phosphoinositide turnover in cell adhesion remains less understood.

Purpose of the Study:

  • To investigate the function of Phospholipase C-gamma1 (PLC-gamma1) in cell adhesion.
  • To elucidate the molecular mechanisms underlying PLC-gamma1's role in integrin-mediated signaling.

Main Methods:

  • Comparison of Plcg1(-/-) fibroblasts (Null) with re-expressed PLC-gamma1 (Null+).
  • Assessment of cell adhesion rates on fibronectin at varying concentrations.
  • Analysis of integrin subunit expression, receptor clustering, and tyrosine phosphorylation sites (Tyr783, Tyr771, Tyr1253) using site-specific antibodies and mutants.
  • Inhibition studies using Src-kinase and epidermal-growth-factor-receptor kinase inhibitors.
  • Co-immunoprecipitation assays to determine protein interactions.

Main Results:

  • Null cells showed significantly impaired adhesion to fibronectin, particularly at low concentrations.
  • PLC-gamma1 tyrosine phosphorylation at Tyr783 was essential for fibronectin-dependent adhesion; mutagenesis of this site abrogated adhesion.
  • The SH2 domains of PLC-gamma1 were required for maximal adhesion.
  • Fibronectin-induced PLC-gamma1 tyrosine phosphorylation was dependent on Src kinase activity and occurred in a FAK-independent manner.
  • PLC-gamma1 directly associated with Src kinase following fibronectin-induced integrin activation.

Conclusions:

  • Phospholipase C-gamma1 plays a critical role in regulating cell adhesion to fibronectin.
  • Src kinase-mediated phosphorylation of PLC-gamma1 at Tyr783 is a key event for integrin-dependent adhesion.
  • PLC-gamma1 functions downstream or independently of FAK in this adhesion pathway, highlighting a novel signaling mechanism involving Src kinase.

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

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

Related Concept Videos

Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Laminins are the Adhesive Proteins of Basal Lamina00:55

Laminins are the Adhesive Proteins of Basal Lamina

Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
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:...