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.
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Authors | Tetsuya Otsuki, Takahiro Nagashima, Norio Komatsu, Keita Kirito, Yusuke Furukawa, Shin-ichi Kobayashi Si, Johnson M Liu, Keiya Ozawa |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 291
Issue 3
Pg. 628-34
(Mar 01 2002)
ISSN: 0006-291X [Print] United States |
PMID | 11855836
(Publication Type: Journal Article)
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Copyright | ©2002 Elsevier Science (USA). |
Chemical References |
- DNA-Binding Proteins
- FANCA protein, human
- Fanconi Anemia Complementation Group A Protein
- Proteins
- Proto-Oncogene Proteins
- AKT1 protein, human
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
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Topics |
- Amino Acid Sequence
- Cell Line
- Consensus Sequence
- DNA-Binding Proteins
- Fanconi Anemia Complementation Group A Protein
- Genetic Complementation Test
- Humans
- Phosphorylation
- Precipitin Tests
- Protein Serine-Threonine Kinases
- Proteins
(chemistry, genetics, metabolism)
- Proto-Oncogene Proteins
(physiology)
- Proto-Oncogene Proteins c-akt
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