title: Phosphorylation of Fanconi anemia protein, FANCA, is regulated by Akt kinase.
abstract: Phosphorylation of the Fanconi anemia complementation group A (FANCA) protein is thought to be important for the function of the FA pathway. However, the kinase for FANCA (so-called FANCA-PK) remains to be identified. FANCA has a consensus sequence for Akt kinase near serine 1149 (Ser1149), suggesting that Akt can phosphorylate FANCA. We performed in vitro kinase assays using as substrate either a GST-fusion wild-type (WT) FANCA fragment or a GST-fusion FANCA fragment containing a mutation from serine to alanine at 1149 (FANCA-S1149A). These experiments confirmed that FANCA is phosphorylated at Ser 1149, in vitro. However, (32)P-orthophosphate labeling experiments revealed that FANCA-S1149A was more efficiently phosphorylated than WT-FANCA. Furthermore, phosphorylation of wild-type FANCA was blocked by coexpression of a constitutively active (CA)-Akt and enhanced by a dominant-negative (DN) Akt. Our results suggest that Akt is a negative regulator of FANCA phosphorylation.
authors.affiliation: Department of Hematology, Center for Molecular Medicine, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Kawachi, Tochigi, 329-0498, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Otsuki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagashima
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
authors.forename: Keita
authors.initials: K
authors.lastname: Kirito
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kobayashi Si
authors.forename: Johnson M
authors.initials: JM
authors.lastname: Liu
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D052217:Fanconi Anemia Complementation Group A Protein; D005816:Genetic Complementation Test; D006801:Humans; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt
chemical_list: D004268:DNA-Binding Proteins; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt