Cytoskeletal organization in tropomyosin-mediated reversion of ras-transformation: Evidence for Rho kinase pathway

Vanya Shah, Shantaram Bharadwaj, Kozo Kaibuchi, G. L. Prasad

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44 Citations (Scopus)

Abstract

Tropomyosin (TM) family of cytoskeletal proteins is implicated in stabilizing actin microfilaments. Many TM isoforms, including tropomyosin-1 (TM1), are down-regulated in transformed cells. Previously we demonstrated that TM1 is a suppressor of the malignant transformation, and that TM1 reorganizes microfilaments in the transformed cells. To investigate how TM1 induces microfilament organization in transformed cells, we utilized ras-transformed NIH3T3 (DT) cells, and those transduced to express TM1, and/or TM2. Enhanced expression of TM1 alone, but not TM2, results in re-emergence of microfilaments; TM1, together with TM2 remarkably improves microfilament architecture. TM1 induced cytoskeletal reorganization involves an enhanced expression of caldesmon, but not vinculin, α-actinin, or gelsolin. In addition, TMl-induced cytoskeletal reorganization and the revertant phenotype appears to involve re-activation of RhoA controlled pathways in DT cells. RhoA expression, which is suppressed in DT cells, is significantly increased in TM1-expressing cells, without detectable changes in the expression of Rac or Cdc42. Furthermore, expression of a dominant negative Rho kinase, or treatment with Y-27632 disassembled microfilaments in normal NIH3T3 and in TM1 expressing cells. These data suggest that reactivation of Rho kinase directed pathways are critical for TMl-mediated microfilament assemblies.

Original languageEnglish
Pages (from-to)2112-2121
Number of pages10
JournalOncogene
Volume20
Issue number17
DOIs
Publication statusPublished - 19-04-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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