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

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

doi:10.1016/j.febslet.2009.11.033

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Volume 584, Issue 1 , Pages 39-43, 4 January 2010

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

Edited by Berend Wieringa

Lu Wang
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Toshiyuki Kobayashi
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Xianghua Piao
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Masatoshi Shiono
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Yumiko Takagi
- Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Reiko Mineki
- Division of Proteomics and BioMolecular Science, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Hikari Taka
- Division of Proteomics and BioMolecular Science, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Danqing Zhang
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Masaaki Abe
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Guodong Sun
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Yoshiaki Hagiwara
- Research and Development, Immuno-Biological Laboratories Co., Ltd., Fujioka-shi, Gunma 375-0005, Japan
Kazuo Okimoto
- Research Administration, Dainippon Sumitomo Pharma Co., Ltd., Osaka 564-0053, Japan
Izumi Matsumoto
- Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka 554-0022, Japan
Mami Kouchi
- Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka 554-0022, Japan
Okio Hino
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
- Corresponding author. Address: Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. Fax: +81 356841646.

Received 29 July 2009; received in revised form 13 October 2009; accepted 9 November 2009. published online 13 November 2009.

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)

Abbreviations: AMPK, 5′-AMP-activated protein kinase, FLCN, folliculin, FNIP, FLCN-interacting protein

Keywords: Birt–Hogg–Dubé syndrome, Folliculin, 5′-AMP-activated protein kinase, Phosphorylation, FLCN-interacting protein