title: Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product.
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.
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Xianghua
authors.initials: X
authors.lastname: Piao
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shiono
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takagi
authors.forename: Reiko
authors.initials: R
authors.lastname: Mineki
authors.forename: Hikari
authors.initials: H
authors.lastname: Taka
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhang
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.forename: Guodong
authors.initials: G
authors.lastname: Sun
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okimoto
authors.forename: Izumi
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Mami
authors.initials: M
authors.lastname: Kouchi
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D045163:Antibodies, Phospho-Specific / Q000096:biosynthesis; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D045163:Antibodies, Phospho-Specific; D002352:Carrier Proteins; C516440:FNIP1 protein, human; C482582:Flcn protein, rat; D011506:Proteins; D012694:Serine; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases