Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation

J. Toshima, J. Y. Toshima, T. Amano, N. Yang, S. Narumiya, K. Mizuno

    Research output: Contribution to journalArticle

    199 Citations (Scopus)

    Abstract

    Testicular protein kinase 1 (TESK1) is a serine/threonine kinase with a structure composed of a kinase domain related to those of LIM-kinases and a unique C-terminal proline-rich domain. Like LIM-kinases, TESK1 phosphorylated cofilin specifically at Ser-3, both in vitro and in vivo. When expressed in HeLa cells, TESK1 stimulated the formation of actin stress fibers and focal adhesions. In contrast to LIM-kinases, the kinase activity of TESK1 was not enhanced by Rho-associated kinase (ROCK) or p21-activated kinase, indicating that TESK1 is not their downstream effector. Both the kinase activity of TESK1 and the level of cofilin phosphorylation increased by plating cells on fibronectin. Y-27632, a specific inhibitor of ROCK, inhibited LIM-kinase-induced cofilin phosphorylation but did not affect fibronectin-induced or TESK1-induced cofilin phosphorylation in HeLa cells. Expression of a kinase-negative TESK1 suppressed cofilin phosphorylation and formation of stress fibers and focal adhesions induced in cells plated on fibronectin. These results suggest that TESK1 functions downstream of integrins and plays a key role in integrin-mediated actin reorganization, presumably through phosphorylating and inactivating cofilin. We propose that TESK1 and LIM-kinases commonly phosphorylate cofilin but are regulated in different ways and play distinct roles in actin reorganization in living cells.

    Original languageEnglish
    Pages (from-to)1131-1145
    Number of pages15
    JournalMolecular Biology of the Cell
    Volume12
    Issue number4
    Publication statusPublished - 2001

    Fingerprint

    Actin Depolymerizing Factors
    Focal Adhesions
    Integrins
    Protein Kinases
    Actins
    Lim Kinases
    Phosphorylation
    Phosphotransferases
    Fibronectins
    rho-Associated Kinases
    Stress Fibers
    HeLa Cells
    testis-specific protein kinase 1
    p21-Activated Kinases
    Protein-Serine-Threonine Kinases
    Proline

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cell Biology

    Cite this

    Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. / Toshima, J.; Toshima, J. Y.; Amano, T.; Yang, N.; Narumiya, S.; Mizuno, K.

    In: Molecular Biology of the Cell, Vol. 12, No. 4, 2001, p. 1131-1145.

    Research output: Contribution to journalArticle

    Toshima, J. ; Toshima, J. Y. ; Amano, T. ; Yang, N. ; Narumiya, S. ; Mizuno, K. / Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. In: Molecular Biology of the Cell. 2001 ; Vol. 12, No. 4. pp. 1131-1145.
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