Regulation of folliculin (the BHD gene product) phosphorylation by Tsc2-mTOR pathway

Xianghua Piao, Toshiyuki Kobayashi, Lu Wang, Masatoshi Shiono, Yumiko Takagi, Guodong Sun, Masaaki Abe, Yoshiaki Hagiwara, Danqing Zhang, Kazuo Okimoto, Mami Kouchi, Izumi Matsumoto, Okio Hino

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    The Birt-Hogg-Dubé gene (BHD) encodes the tumor suppressor protein folliculin (FLCN). The function of FLCN has recently been implicated in the regulation of rapamycin-sensitive mTOR complex (mTORC1). Reciprocally, the mTORC1-dependent phosphorylation of FLCN was reported. However, precise mechanism of FLCN phosphorylation and functional interaction of FLCN with tuberin, the product of tuberous sclerosis 2 gene (TSC2) which is a negative regulator of mTORC1, are unclear. Here we report that multiple phosphorylation in FLCN are evoked by downregulation of tuberin as well as by Rheb expression. We found that phosphorylation at Ser62 and Ser302 are differently regulated by mTORC1-dependent pathway. Some unknown kinases downstream of tuberin-mTORC1 are thought to directly phosphorylate FLCN. Interestingly, our results also suggest that the complex formation of FLCN with AMPK is modulated by FLCN phosphorylation. These results suggest that FLCN is involved in a novel mechanism of signal transduction downstream of tuberin.

    Original languageEnglish
    Pages (from-to)16-21
    Number of pages6
    JournalBiochemical and biophysical research communications
    Volume389
    Issue number1
    DOIs
    Publication statusPublished - 2009 Nov 6

    Keywords

    • AMPK
    • BHD
    • FLCN
    • Phosphorylation
    • Rheb
    • S6K
    • Tsc2
    • mTOR

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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