Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product

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

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    Recently, it was reported that the product of Birt-Hogg-Dubé syndrome gene (folliculin, FLCN) is directly phosphorylated by 5′-AMP-activated protein kinase (AMPK). In this study, we identified serine 62 (Ser62) as a phosphorylation site in FLCN and generated an anti-phospho-Ser62-FLCN antibody. Our analysis suggests that Ser62 phosphorylation is indirectly up-regulated by AMPK and that another residue is directly phosphorylated by AMPK. By binding with FLCN-interacting proteins (FNIP1 and FNIP2/FNIPL), Ser62 phosphorylation is increased. A phospho-mimic mutation at Ser62 enhanced the formation of the FLCN-AMPK complex. These results suggest that function(s) of FLCN-AMPK-FNIP complex is regulated by Ser62 phosphorylation. Structured summary: MINT-7298145, MINT-7298166: Flcn (uniprotkb:Q76JQ2) physically interacts (MI:0915) with AMPK alpha 1 (uniprotkb:P54645) by anti tag coimmunoprecipitation (MI:0007). MINT-7298267: AMPK alpha 1 (uniprotkb:Q13131) phosphorylates (MI:0217) tsc2 (uniprotkb:P49816) by protein kinase assay (MI:0424). MINT-7298182: FNIP1 (uniprotkb:Q8TF40) physically interacts (MI:0915) with Flcn (uniprotkb:Q76JQ2) by anti tag coimmunoprecipitation (MI:0007). MINT-7298132: AMPK alpha 1 (uniprotkb:Q13131) phosphorylates (MI:0217) Flcn (uniprotkb:Q76JQ2) by protein kinase assay (MI:0424). MINT-7298229: FNIPL (uniprotkb:Q9P278) physically interacts (MI:0915) with Flcn (uniprotkb:Q76JQ2) by anti tag coimmunoprecipitation (MI:0007).

    Original languageEnglish
    Pages (from-to)39-43
    Number of pages5
    JournalFEBS Letters
    Volume584
    Issue number1
    DOIs
    Publication statusPublished - 2010 Jan 4

    Keywords

    • 5′-AMP-activated protein kinase
    • Birt-Hogg-Dubé syndrome
    • FLCN-interacting protein
    • Folliculin
    • Phosphorylation

    ASJC Scopus subject areas

    • Biophysics
    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics
    • Cell Biology

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  • Cite this

    Wang, L., Kobayashi, T., Piao, X., Shiono, M., Takagi, Y., Mineki, R., Taka, H., Zhang, D., Abe, M., Sun, G., Hagiwara, Y., Okimoto, K., Matsumoto, I., Kouchi, M., & Hino, O. (2010). Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product. FEBS Letters, 584(1), 39-43. https://doi.org/10.1016/j.febslet.2009.11.033