[Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption].
We have previously shown that microtubule disruption results in an increase in cell adhesion to ECM proteins. In this work we show that this enhanced cell attachment was completely abolished by specific inhibitors of tyrosine-kinases, PI3-K and PKCs. Microtubule depolymerisation was associated with an important increased in tyrosine phosphorylation of FAK and paxilline, as well as with subcellular localisation of PKCgamma, delta and epsilon. We also observed significant alterations in actin cytoskeleton leading to reduced cell spreading. Thus, microtubule depolymerisation appears to activate various intracellular kinases that lead to actin cytoskeletal changes and to an increase of integrin-dependent adhesion. Whether this enhanced attachment is due to intracellular events resulting in changes in integrin affinity or avidity remains to be determined.
Kadi
Azzeddine
A
Laboratoire de biochimie cellulaire, CNRS UMR 6032, Faculté de Pharmacie, 27, bd Jean-Moulin, 13385 Marseille Cedex 5.
Berthet
Virginie
V
Pichard
Véronique
V
Abadie
Brigitte
B
Rognoni
Jean-Baptiste
JB
Marvaldi
Jacques
J
Luis
José
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D051418:Focal Adhesion Kinase 2; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C103547:PTK2B protein, human; D011493:Protein Kinase C; D017239:Paclitaxel; D000077235:Vinorelbine; D015739:Nocodazole