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Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2.
- Source :
-
Journal of cell science [J Cell Sci] 2010 Mar 15; Vol. 123 (Pt 6), pp. 983-92. - Publication Year :
- 2010
-
Abstract
- Protein kinases AKT and PKBR1 of Dictyostelium belong to the AGC protein kinase superfamily. AKT and PKBR1 are phosphorylated at similar sites by phosphoinositide-dependent kinase 1 (PDK1) and TORC2 kinases; however, they have different subcellular localizing domains. AKT has a phosphoinositide 3-kinase (PI3K)/phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)]-regulated PH (pleckstrin homology) domain whereas PKBR1 is myristoylated and persistently membrane localized. Using strains defective for PI3K/PtdIns(3,4,5)P(3)-, PDK1- and TORC2-signaling or strains that express phospho-site mutants of AKT and PKBR1, we dissect the different roles of PI3K/PtdIns(3,4,5)P(3), PDK1 and TORC2. We show that activation of AKT and PKBR1 requires PDK1-site phosphorylation, but that phosphorylation by TORC2 is insufficient for AKT or PKBR1 activation. However, PDK1-site phosphorylation is dependent on phosphorylation by TORC2, which suggests that there is regulatory coordination among PDK1, TORC2 and their phospho-site targets. This defines a separate input for signaling in control of chemotaxis and dependency on PDK1 function. We also demonstrate that PDK1 in Dictyostelium functions independently of PI3K/PtdIns(3,4,5)P(3). Finally, we show that AKT and PKBR1 exhibit substrate selectivity and identify two novel lipid-interacting proteins preferentially phosphorylated by AKT. Despite certain similarities, AKT and PKBR1 have distinct regulatory paths that impact activation and effector targeting, with PDK1 serving a central role.
- Subjects :
- 3-Phosphoinositide-Dependent Protein Kinases
Amino Acid Motifs
Animals
Chemotactic Factors pharmacology
Cyclic AMP pharmacology
Dictyostelium drug effects
Enzyme Activation drug effects
Folic Acid pharmacology
Lipid Metabolism drug effects
Phosphatidylinositol 3-Kinases metabolism
Phosphatidylinositol Phosphates metabolism
Phosphorylation drug effects
Signal Transduction drug effects
Substrate Specificity drug effects
Chemotaxis drug effects
Dictyostelium cytology
Dictyostelium enzymology
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Protozoan Proteins metabolism
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 123
- Issue :
- Pt 6
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 20200230
- Full Text :
- https://doi.org/10.1242/jcs.064022