Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product.
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.
Wang
Lu
L
Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
Kobayashi
Toshiyuki
T
Piao
Xianghua
X
Shiono
Masatoshi
M
Takagi
Yumiko
Y
Mineki
Reiko
R
Taka
Hikari
H
Zhang
Danqing
D
Abe
Masaaki
M
Sun
Guodong
G
Hagiwara
Yoshiaki
Y
Okimoto
Kazuo
K
Matsumoto
Izumi
I
Kouchi
Mami
M
Hino
Okio
O
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*
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