| c-Abl tyrosine kinase regulates serum-induced nuclear export of diacylglycerol kinase α by phosphorylation at Tyr-218. | |
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MedLine Citation:
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PMID: 22199356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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c-Abl is a tyrosine kinase involved in many cellular processes, including cell cycle control and proliferation. However, little is known about its substrates. Here, we show that c-Abl directly phosphorylates diacylglycerol kinase α (DGKα), an important regulator of many cellular events through its conversion of diacylglycerol to phosphatidic acid. We found that DGKα was transported from the cytoplasm to the nucleus in response to serum starvation, and serum restoration induced the nuclear export of the enzyme to the cytoplasm. This serum-induced export involves two tyrosine kinases, c-Src and c-Abl. The latter, c-Abl, is activated by c-Src, phosphorylates DGKα, and shuttles between the nucleus and the cytoplasm in a direction opposite to that of DGKα in response to serum restoration. Moreover, an in vitro phosphorylation assay using purified mutants of DGKα identified Tyr-218 as a site of phosphorylation by c-Abl. We confirmed these results for endogenous DGKα using an antibody specific for phospho-Tyr-218, and this phosphorylation was necessary for the serum-induced export of DGKα. These results demonstrate that the nucleo-cytoplasmic shuttling of DGKα is orchestrated by tyrosine phosphorylation by the Src-activated tyrosine kinase c-Abl and that this phosphorylation is important for regulating the function of cytoplasmic and/or nuclear DGKα. |
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Authors:
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Takehiro Matsubara; Momo Ikeda; Yuko Kiso; Megumi Sakuma; Ken-ichi Yoshino; Fumio Sakane; Isabel Merida; Naoaki Saito; Yasuhito Shirai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-12-23 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-21 Completed Date: 2012-04-09 Revised Date: 2013-04-12 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 5507-17 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Rokkodai-cho 1-1, Nada-ku, Kobe 657-8501, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Animals Binding Sites COS Cells Cell Nucleus / metabolism* Cercopithecus aethiops Diacylglycerol Kinase / chemistry*, metabolism* Mice NIH 3T3 Cells Phosphorylation Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins c-abl / metabolism* Serum / metabolism* Swine Tyrosine* |
| Chemical | |
Reg. No./Substance:
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55520-40-6/Tyrosine; EC 2.7.1.107/Diacylglycerol Kinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/CSK tyrosine-protein kinase; EC 2.7.10.2/Proto-Oncogene Proteins c-abl |
| Comments/Corrections | |
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