Allosteric activation of the protein kinase PDK1 with low molecular weight compounds

EMBO Journal

Volumn 25, Issue 23, 2006, Pages 5469-5480

  Engel, Matthias ^a   Hindie, Valerie ^b,c   Lopez Garcia, Laura A ^b   Stroba, Adriana ^a   Schaeffer, Francis ^c   Adrian, Iris ^b   Imig, Jochen ^b   Idrissova, Leila ^b   Nastainczyk, Wolfgang ^b   Zeuzem, Stefan ^b   Alzari, Pedro M ^c   Hartmann, Rolf W ^a   Piiper, Albrecht ^b   Biondi, Ricardo M ^b  

^a SAARLAND UNIVERSITY   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

^c INSTITUT PASTEUR   (France)

Author keywords

AGC kinase; PDK1; PIF pocket; Protein conformation; Protein phosphorylation

Indexed keywords

AGC KINASE; AMINO ACID; ENZYME ACTIVATOR; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1 ACTIVATOR; PHOSPHOTRANSFERASE; PROTEIN KINASE;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; CONFORMATIONAL TRANSITION; DRUG MECHANISM; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HYDROPHOBICITY; ISOTHERMAL TITRATION CALORIMETRY; MOLECULAR WEIGHT; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION;

ACETIC ACIDS; ALLOSTERIC REGULATION; AMINO ACID MOTIFS; BINDING SITES; CELLS, CULTURED; DRUG DESIGN; ENZYME ACTIVATION; HUMANS; HYDROPHOBICITY; MOLECULAR WEIGHT; MUTATION; PHOSPHOPEPTIDES; PHOSPHORYLATION; PROTEIN CONFORMATION; PROTEIN-SERINE-THREONINE KINASES;

EID: 33751583820     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/sj.emboj.7601416     Document Type: Article

References (31)

1. Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (2000) A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta) and PKC-related kinase 2 by PDK1. J Biol Chem 275: 20806-20813
2. Biondi RM (2004) Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation. Trends Biochem Sci 29: 136-142
3. Biondi RM, Cheung PC, Casamayor A, Deak M, Currie RA, Alessi DR (2000) Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA. EMBO J 19: 979-988
4. Biondi RM, Kieloch A, Currie RA, Deak M, Alessi DR (2001) The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. EMBO J 20: 4380-4390
5. Biondi RM, Komander D, Thomas CC, Lizcano JM, Deak M, Alessi DR, van Aalten DM (2002) High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. EMBO J 21: 4219-4228
6. Biondi RM, Nebreda AR (2003) Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. Biochem J 372: 1-13
7. Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411: 355-365
8. Cohen P (2002) Protein kinases - the major drug targets of the twenty-first century? Nat Rev Drug Discov 1: 309-315
9. Collins BJ, Deak M, Arthur JS, Armit LJ, Alessi DR (2003) In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation. EMBO J 22: 4202-4211
10. Collins BJ, Deak M, Murray-Tait V, Storey KG, Alessi DR (2005) In vivo role of the phosphate groove of PDK1 defined by knockin mutation. J Cell Sci 118: 5023-5034
11. Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH (2001) Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 105: 721-732
12. Etchebehere LC, Van Bemmelen MX, Anjard C, Traincard F, Assemat K, Reymond C, Veron M (1997) The catalytic subunit of Dictyostelium cAMP-dependent protein kinase - role of the N-terminal domain and of the C-terminal residues in catalytic activity and stability. Eur J Biochem 248: 820-826
13. Frame S, Cohen P, Biondi RM (2001) A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell 7: 1321-1327
14. Frodin M, Antal TL, Dummler BA, Jensen CJ, Deak M, Gammeltoft S, Biondi RM (2002) A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation. EMBO J 21: 5396-5407
15. Frodin M, Jensen CJ, Merienne K, Gammeltoft S (2000) A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J 19: 2924-2934
16. Gonfloni S, Williams JC, Hattula K, Weijland A, Wierenga RK, Superti-Furga G (1997) The role of the linker between the SH2 domain and catalytic domain in the regulation and function of Src. EMBO J 16: 7261-7271
17. Huang X, Begley M, Morgenstern KA, Gu Y, Rose P, Zhao H, Zhu X (2003) Crystal structure of an inactive akt2 kinase domain. Structure (Cambridge) 11: 21-30
18. Huse M, Kuriyan J (2002) The conformational plasticity of protein kinases. Cell 109: 275-282
19. Johnson LN, Lewis RJ (2001) Structural basis for control by phosphorylation. Chem Rev 101: 2209-2242
20. Knighton DR, Xuong NH, Taylor SS, Sowadski JM (1991) Crystallization studies of cAMP-dependent protein kinase. cocrystals of the catalytic subunit with a 20 amino acid residue peptide inhibitor and MgATP diffract to 3.0 A resolution. J Mol Biol 220: 217-220
21. Komander D, Kular G, Deak M, Alessi DR, van Aalten DM (2005) Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding. J Biol Chem 280: 18797-18802
22. Newton AC (2003) Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J 370: 361-371
23. Parker PJ, Parkinson SJ (2001) AGC protein kinase phosphorylation and protein kinase C. Biochem Soc Trans 29: 860-863
24. Pawson T, Scott JD (2005) Protein phosphorylation in signaling - 50 years and counting. Trends Biochem Sci 30: 286-290
25. Pearl LH, Barford D (2002) Regulation of protein kinases in insulin, growth factor and Wnt signalling. Curr Opin Struct Biol 12: 761-767
26. Schaeffer F, Matuschek M, Guglielmi G, Miras I, Alzari PM, Beguin P (2002) Duplicated dockerin subdomains of Clostridium thermocellum endoglucanase CelD bind to a cohesin domain of the scaffolding protein CipA with distinct thermodynamic parameters and a negative cooperativity. Biochemistry 41: 2106-2114
27. Sicheri F, Moarefi I, Kuriyan J (1997) Crystal structure of the Src family tyrosine kinase Hck. Nature 385: 602-609
28. Smith KJ, Carter PS, Bridges A, Horrocks P, Lewis C, Pettman G, Clarke A, Brown M, Hughes J, Wilkinson M, Bax B, Reith A (2004) The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein. Structure (Cambridge) 12: 1067-1077
29. Xu W, Harrison SC, Eck MJ (1997) Three-dimensional structure of the tyrosine kinase c-Src. Nature 385: 595-602
30. Xu ZB, Chaudhary D, Olland S, Wolfrom S, Czerwinski R, Malakian K, Lin L, Stahl ML, Joseph-McCarthy D, Benander C, Fitz L, Greco R, Somers WS, Mosyak L (2004) Catalytic domain crystal structure of protein kinase C-theta (PKCtheta). J Biol Chem 279: 50401-50409
31. Yang J, Cron P, Thompson V, Good VM, Hess D, Hemmings BA, Barford D (2002) Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Mol Cell 9: 1227-1240