Related Experiment Video

Updated: Aug 2, 2026

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones
09:14

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones

Published on: March 17, 2011

Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins

I Ivankovic-Dikic1, E Grönroos, A Blaukat

  • 1Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S- 75124, Sweden. Ivan.Dikic@licr.uu.se

Nature Cell Biology
|September 12, 2000
PubMed

Insights

Focal-adhesion kinase (FAK) family members Pyk2 and FAK are crucial for neurite outgrowth in neuronal cells. Their activation by co-stimulated growth-factor and integrin receptors integrates signals essential for neuronal development.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Biology

Background:

  • Signaling pathways from receptor tyrosine kinases and integrins are vital for cellular responses.
  • Neurite outgrowth is a fundamental process in neuronal development and function.

Purpose of the Study:

  • To investigate the role of the focal-adhesion kinase (FAK) family in integrating signals for neurite outgrowth.
  • To elucidate the mechanism by which growth factor and integrin signaling converge to regulate neuronal morphology.

Main Methods:

  • Co-stimulation of growth-factor receptors and integrins in PC12 and SH-SY5Y cells.
  • Analysis of Pyk2 and FAK association with adhesion complexes containing epidermal growth factor (EGF) receptors.
  • Assessment of neurite outgrowth and extracellular-signal-regulated kinase (ERK) activation upon expression of FAK/Pyk2 domains.

Main Results:

  • Co-stimulation activated the FAK family (Pyk2 and FAK), promoting neurite outgrowth.
  • Pyk2 and FAK associate with EGF receptor-containing adhesion complexes via their terminal domains.
  • Expression of FAK/Pyk2 C-terminal domains inhibited neurite outgrowth but not ERK activation.
  • Activation and autophosphorylation of Pyk2/FAK and paxillin were critical for neurite formation signaling.

Conclusions:

  • Pyk2 and FAK play essential roles in signal integration at the interface of integrin and growth-factor receptor complexes in neurons.
  • The FAK family acts as a critical mediator linking adhesion and growth factor signaling to control neurite outgrowth.

More Related Videos

Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy05:50

Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy

Published on: November 1, 2021

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance07:53

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance

Published on: October 21, 2021

Related Concept Videos

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...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...