دورية أكاديمية
Fine tuning PDK1 activity by phosphorylation at Ser163.
| العنوان: | Fine tuning PDK1 activity by phosphorylation at Ser163. |
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| المؤلفون: | Riojas RA; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229., Kikani CK; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229., Wang C; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229., Mao X; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229., Zhou L; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229., Langlais PR; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229., Hu D; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229., Roberts JL; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229; Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78229., Dong LQ; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229; Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78229; Departments of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229., Liu F; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229; Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229; Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78229. Electronic address: liuf@uthscsa.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2006 Aug 04; Vol. 281 (31), pp. 21588-21593. Date of Electronic Publication: 2006 Jun 02. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Protein Serine-Threonine Kinases/*metabolism , Serine/*metabolism, 3-Phosphoinositide-Dependent Protein Kinases ; Amino Acid Substitution ; Animals ; Binding Sites ; Cell Line ; Humans ; Hydrogen Bonding ; Insulin/pharmacology ; Mice ; Models, Molecular ; Phosphorylation ; Protein Serine-Threonine Kinases/chemistry ; Sequence Alignment ; Transfection |
| مستخلص: | 3-Phosphoinositide-dependent protein kinase-1 (PDK1) mediates phosphorylation and activation of members of the AGC protein kinase family and plays an essential role in insulin signaling and action. However, whether and how PDK1 activity is regulated in cells remains largely uncharacterized. In the present study, we show that PDK1 undergoes insulin-stimulated and phosphatidylinositol 3-kinase-dependent phosphorylation at Ser244 in the activation loop and at a novel site: Ser163 in the hinge region between the two lobes of the kinase domain. Sequence alignment studies revealed that the residue corresponding to Ser163 of PDK1 in all other AGC kinases is glutamate, suggesting that a negative charge at this site may be important for PDK1 function. Replacing Ser163 with a negatively charged residue, glutamate, led to a 2-fold increase in PDK1 activity. Molecular modeling studies suggested that phosphorylated Ser163 may form additional hydrogen bonds with Tyr149 and Gln223. In support of this, mutation of Tyr149 to Ala is sufficient to reduce PDK1 activity. Taken together, our results suggest that PDK1 phosphorylation of Ser163 may provide a mechanism to fine-tune PDK1 activity and function in cells. |
| معلومات مُعتمدة: | F31DK068874 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Insulin) 452VLY9402 (Serine) EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases) EC 2.7.11.1 (PDPK1 protein, human) EC 2.7.11.1 (Pdpk1 protein, mouse) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20060606 Date Completed: 20061016 Latest Revision: 20211203 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1074/jbc.M600393200 |
| PMID: | 16751192 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0021-9258 |
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| DOI: | 10.1074/jbc.M600393200 |