Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding

    Authors

    C. Thaxton; J. Lopera; M. Bott; M. E. Baldwin; P. Kalidas;C. Fernandez-Valle

    Comments

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    Abbreviated Journal Title

    Mol. Cell. Neurosci.

    Keywords

    schwannomin; merlin; Rac; FOCAL ADHESION KINASE; NEUROFIBROMATOSIS TYPE-2; P21-ACTIVATED KINASE; F-ACTIN; PLASMA-MEMBRANE; GENE-PRODUCT; MERLIN PHOSPHORYLATION; GROWTH; SUPPRESSION; TERMINAL DOMAIN; PROTEIN; Neurosciences

    Abstract

    Mutations in the Neurofibromatosis type 2 tumor suppressor gene that encodes Schwannomin causes formation of benign schwannomas. Schwannoma cells lose their characteristic bipolar shape and become rounded with excessive ruffling membranes. Schwannomin is phosphorylated at serine 518 (S518) by p21 activated kinase (Pak). Unphosphorylated schwannomin is associated with growth inhibition but little is known about the function of the phosphorylated form, or the molecular events leading to its phosphorylation. Here, we report in SCs that schwannomin S518 phosphorylation requires binding to paxillin and targeting to the plasma membrane. Phospho-S518-schwannomin is enriched in the peripheral-most aspects of membrane specializations where paxillin, activated Pak, Cdc42 but not Rac are highly expressed. Schwannomin and Pak phosphorylation levels are not reduced in response to lowering Rac-GTP levels with NSC23766. Expression of schwannomin S518A/D-GFP variants each distinctively altered Schwann cell shape and polarity. These results are consistent with tight spatial regulation of S518 phosphorylation at the plasma membrane in a paxillin and Cdc42-Pak dependent manner that leads to local reorganization of the SC cytoskeleton. (c) 2006 Elsevier Inc. All rights reserved.

    Journal Title

    Molecular and Cellular Neuroscience

    Volume

    34

    Issue/Number

    2

    Publication Date

    1-1-2007

    Document Type

    Article

    Language

    English

    First Page

    231

    Last Page

    242

    WOS Identifier

    WOS:000244073000011

    ISSN

    1044-7431

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