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c-Abl Tyrosine Kinase Regulates Serum-induced Nuclear Export of Diacylglycerol Kinase α by Phosphorylation at Tyr-218
- Source :
- Journal of Biological Chemistry. 287:5507-5517
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- 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.
- Subjects :
- Serum
Diacylglycerol Kinase
Swine
Mutant
Active Transport, Cell Nucleus
Biology
Biochemistry
CSK Tyrosine-Protein Kinase
Mice
chemistry.chemical_compound
hemic and lymphatic diseases
Chlorocebus aethiops
Animals
Phosphorylation
Proto-Oncogene Proteins c-abl
Nuclear export signal
neoplasms
Molecular Biology
Diacylglycerol kinase
Cell Nucleus
Binding Sites
Tyrosine phosphorylation
Cell Biology
Phosphatidic acid
Protein-Tyrosine Kinases
src-Family Kinases
chemistry
Cytoplasm
COS Cells
NIH 3T3 Cells
Tyrosine
Tyrosine kinase
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....9072add1e60190476b9566707c350432
- Full Text :
- https://doi.org/10.1074/jbc.m111.296897