[Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption]

Azzeddine Kadi1, Virginie Berthet, Véronique Pichard

  • 1Laboratoire de biochimie cellulaire, CNRS UMR 6032, Faculté de Pharmacie, 27, bd Jean-Moulin, 13385 Marseille Cedex 5.

Bulletin Du Cancer
|March 13, 2002
PubMed

Insights

Microtubule disruption increases cell adhesion by activating intracellular kinases, but this effect is blocked by specific inhibitors. Further research is needed to understand the exact mechanisms behind this enhanced cell attachment.

Area of Science:

  • Cell biology
  • Biochemistry
  • Molecular biology

Background:

  • Microtubule disruption is known to increase cell adhesion to extracellular matrix (ECM) proteins.
  • The precise molecular mechanisms underlying this phenomenon require further elucidation.

Purpose of the Study:

  • To investigate the intracellular signaling pathways involved in enhanced cell adhesion following microtubule disruption.
  • To identify key kinases and cellular changes associated with increased cell attachment.

Main Methods:

  • Utilized specific inhibitors of tyrosine-kinases, PI3-K (Phosphoinositide 3-kinase), and PKCs (Protein Kinase Cs).
  • Assessed tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin.
  • Examined the subcellular localization of PKC isoforms (gamma, delta, epsilon).
  • Analyzed alterations in the actin cytoskeleton and cell spreading.

Main Results:

  • Enhanced cell attachment due to microtubule depolymerization was abolished by tyrosine-kinase, PI3-K, and PKC inhibitors.
  • Microtubule depolymerization increased tyrosine phosphorylation of FAK and paxillin.
  • Specific PKC isoforms translocated to the cell interior.
  • Actin cytoskeleton changes led to reduced cell spreading.

Conclusions:

  • Microtubule depolymerization activates intracellular kinases, leading to actin cytoskeletal alterations and increased integrin-dependent cell adhesion.
  • The enhanced attachment may involve changes in integrin affinity or avidity, warranting further investigation.

Related Concept Videos

Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
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...
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...