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Regulation of the Interaction between Protein Kinase C-related Protein Kinase 2 (PRK2) and Its Upstream Kinase, 3-Phosphoinositide-dependent Protein Kinase 1 (PDK1)
Regulation of the Interaction between Protein Kinase C-related Protein Kinase 2 (PRK2) and Its Upstream Kinase, 3-Phosphoinositide-dependent Protein Kinase 1 (PDK1)
- Source :
- Journal of Biological Chemistry. 284:30318-30327
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do not apply for other AGC kinases.
- Subjects :
- Models, Molecular
animal structures
Protein Serine-Threonine Kinases
Mitogen-activated protein kinase kinase
Biochemistry
Cell Line
MAP2K7
3-Phosphoinositide-Dependent Protein Kinases
Humans
ASK1
c-Raf
Phosphorylation
Protein kinase A
Molecular Biology
Protein Kinase C
Binding Sites
biology
MAP kinase kinase kinase
Chemistry
Mechanisms of Signal Transduction
Cyclin-dependent kinase 2
Cell Biology
biology.protein
Cyclin-dependent kinase 9
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....9dcf02f99c93f296be4a02532cfcb4be
- Full Text :
- https://doi.org/10.1074/jbc.m109.051151