TY - JOUR
T1 - Serine 62 is a phosphorylation site in folliculin, the Birt-Hogg-Dubé gene product
AU - Wang, Lu
AU - Kobayashi, Toshiyuki
AU - Piao, Xianghua
AU - Shiono, Masatoshi
AU - Takagi, Yumiko
AU - Mineki, Reiko
AU - Taka, Hikari
AU - Zhang, Danqing
AU - Abe, Masaaki
AU - Sun, Guodong
AU - Hagiwara, Yoshiaki
AU - Okimoto, Kazuo
AU - Matsumoto, Izumi
AU - Kouchi, Mami
AU - Hino, Okio
N1 - Funding Information:
We thank Dr. N. Oshiro (Kobe University) and Dr. T. Maeda (Tokyo University) for their advices on experiments and Dr. M. Maeda (IBL) for antibody preparation. This work was supported by the Research Institute for Diseases of Old Age of the Juntendo University, a Grant-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Ministry of Health, Labour and Welfare.
PY - 2010/1/4
Y1 - 2010/1/4
N2 - 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).
AB - 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).
KW - 5′-AMP-activated protein kinase
KW - Birt-Hogg-Dubé syndrome
KW - FLCN-interacting protein
KW - Folliculin
KW - Phosphorylation
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U2 - 10.1016/j.febslet.2009.11.033
DO - 10.1016/j.febslet.2009.11.033
M3 - Article
C2 - 19914239
AN - SCOPUS:71549132196
VL - 584
SP - 39
EP - 43
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -