Related Experiment Video

Updated: Jun 27, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

alpha- and gamma-Protocadherins negatively regulate PYK2

Jian Chen1, Yanyan Lu1, Shuxia Meng1

  • 1Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208.

The Journal of Biological Chemistry
|December 3, 2008
PubMed

Insights

Gamma-protocadherins (PCDH-gamma) regulate neuronal survival by inhibiting tyrosine kinases PYK2 and FAK. This discovery reveals a new signaling pathway for protocadherins in the central nervous system.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Gamma-protocadherins (PCDH-gamma) are crucial for neuronal survival and synaptic connections in the central nervous system.
  • The intracellular signaling pathways regulated by PCDH-gamma remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the intracellular signaling mechanisms of PCDH-gamma.
  • To investigate the interaction between PCDH-gamma and intracellular kinases.
  • To understand the role of these interactions in neuronal survival.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Kinase activity assays.
  • Overexpression studies in chicken spinal cord neurons.

Main Results:

  • PCDH-gamma directly binds to tyrosine kinases PYK2 and FAK, inhibiting their activity.
  • PYK2 activity is elevated in PCDH-gamma-deficient neurons.
  • Overexpression of PYK2 leads to apoptosis.
  • PCDH-alpha also interacts with PYK2 and FAK, forming functional complexes with PCDH-gamma.

Conclusions:

  • PCDH-gamma negatively regulates PYK2 activity, contributing to neuronal survival.
  • PCDH-alpha and PCDH-gamma converge distinct extracellular signals into common intracellular pathways via PYK2 and FAK.
  • This study identifies PYK2 and FAK as common intracellular effectors for protocadherin signaling.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis07:26

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis

Published on: April 1, 2022

Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
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...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.