title: Involvement of microtubules in the control of adhesion-dependent signal transduction.
abstract: BACKGROUND
  The adhesion of cells to the extracellular matrix (ECM) generates transmembrane signals that affect cell proliferation, differentiation and survival. These signals are triggered by interactions between integrin and the ECM and involve tyrosine phosphorylation of specific proteins, including focal adhesion kinase (FAK) and paxillin, and the assembly of focal adhesions and actin bundles. In matrix-adherent, serum-starved Swiss 3T3 cells, the system of focal adhesions and actin bundles is poorly developed, and the level of tyrosine phosphorylation of FAK and paxillin is low. A number of growth factors rapidly stimulate tyrosine phosphorylation of these proteins and the assembly of focal adhesions and actin bundles. Growth factors and adhesion to the ECM are both necessary for the subsequent transition of cells to the S-phase of the cell cycle.
  
  
  RESULTS
  In serum-starved Swiss 3T3 cells, the disruption of microtubules by nocodazole or vinblastine, without the addition of external growth factors, induces the rapid assembly of focal adhesions and microfilament bundles, tyrosine phosphorylation of FAK and paxillin, and subsequent enhancement of DNA synthesis. All these effects require cell adhesion to the ECM and do not occur when cells are plated on substrates coated with poly-L-lysine or concanavalin A. Inhibitors of tyrosine phosphorylation and cell contractility also eliminate the effects of microtubule disruption on adhesion-dependent signal transduction.
  
  
  CONCLUSIONS
  In ECM-attached cells, microtubule disruption activates the integrin-dependent signaling cascade, which leads to the assembly of matrix adhesions and the induction of DNA synthesis. The increase in cell contractility is an indispensable intermediate step in this signaling process.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Bershadsky
authors.forename: A
authors.initials: A
authors.lastname: Chausovsky
authors.forename: E
authors.initials: E
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Lyubimova
authors.forename: B
authors.initials: B
authors.lastname: Geiger
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019833:Genistein; D007211:Indoles; D016023:Integrins / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D016023:Integrins; D007529:Isoflavones; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; C063769:KT 5926; D014443:Tyrosine; D014747:Vinblastine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D017239:Paclitaxel; D015739:Nocodazole