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Curr Biol. 1996 Oct 1;6(10):1279-89.

Involvement of microtubules in the control of adhesion-dependent signal transduction.

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1
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

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.

PMID:
8939572
[Indexed for MEDLINE]
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