Title:
METHODS FOR ALTERING SUBSTRATE SPECIFICITY OF PHOSPHOINOSITIDE-DEPENDENT-PROTEIN KINASE 1 (PDK1)
Document Type and Number:
WIPO Patent Application WO2000056864
Kind Code:
A3
Abstract:
A method of altering the substrate specificity of phosphoinositide-dependent protein kinase 1 (PDK1) wherein the said PDK1 is exposed to a polypeptide which comprises the amino acid sequence Phe/Tyr-Xaa-Xaa-Phe/Tyr-Zaa-Phe/Tyr wherein Zaa represents a negatively charged amino acid residue. The PDK1 with altered substrate specificity is capable of phosphorylating the underlined residue in a polypeptide with an amino acid sequence corresponding to the consensus sequence Phe/Tyr-Xaa-Xaa-Phe/Tyr-Ser/Thr-Phe/Tyr. The PDK1 with altered specificity may be useful in screening assays and for phosphorylating substrates having the above consensus sequence.
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Inventors:
ALESSI DARIO (GB)
BALENDRAN ANUDHARAN (GB)
DEAK MARIA (GB)
CURRIE RICHARD (GB)
DOWNES PETER (GB)
CASAMAYOR ANTONIO (US)
BALENDRAN ANUDHARAN (GB)
DEAK MARIA (GB)
CURRIE RICHARD (GB)
DOWNES PETER (GB)
CASAMAYOR ANTONIO (US)
Application Number:
PCT/GB2000/001004
Publication Date:
January 18, 2001
Filing Date:
March 17, 2000
Export Citation:
Assignee:
UNIV DUNDEE (GB)
ALESSI DARIO (GB)
BALENDRAN ANUDHARAN (GB)
DEAK MARIA (GB)
CURRIE RICHARD (GB)
DOWNES PETER (GB)
CASAMAYOR ANTONIO (US)
ALESSI DARIO (GB)
BALENDRAN ANUDHARAN (GB)
DEAK MARIA (GB)
CURRIE RICHARD (GB)
DOWNES PETER (GB)
CASAMAYOR ANTONIO (US)
International Classes:
G01N33/50; A61K38/00; A61K45/00; A61P5/50; A61P43/00; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N9/12; C12N15/09; C12Q1/48; G01N33/15; G01N33/573; (IPC1-7): C12N9/12; C12Q1/48; C07K14/47; C12N15/63; C12N5/10; C12S3/14; C07K1/113; C07K19/00; A61P43/00
Domestic Patent References:
| WO1998041638A1 | 1998-09-24 |
Foreign References:
| US6001622A | 1999-12-14 |
Other References:
LE GOOD A.J. ET AL.: "Protein Kinase C Isotypes Controlled by Phosphoinositide 3-Kinase Through the Protein Kinase PDK1", SCIENCE, vol. 281, 25 September 1998 (1998-09-25), pages 2042 - 2045, XP002147843
PALMER R.H. ET AL.: "Expression, purification and characterization of the ubiquitous protein kinase C-related kinase 1.", BIOCHEMICAL JOURNAL, vol. 309, no. 1, 1 July 1995 (1995-07-01), pages 315 - 320, XP000925935
BALENDRAN A. ET AL.: "PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus", CURRENT BIOLOGY, vol. 9, no. 8, 22 April 1999 (1999-04-22), pages 393 - 404, XP000925908
VANHAESEBROECK B. ET AL.: "The PI3K-PDK1 connection: more than just a road to PKB", BIOCHEMICAL JOURNAL, vol. 346, no. 3, 15 March 2000 (2000-03-15), pages 561 - 576, XP000925911
BIONDI R.M. ET AL.: "Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA", THE EMBO JOURNAL, vol. 19, no. 5, 1 March 2000 (2000-03-01), pages 979 - 988, XP002147844
BELHAM C. ET AL.: "Intracellular signalling: PDK1--a kinase at the hub of things", CURRENT BIOLOGY, vol. 9, no. 3, 11 February 1999 (1999-02-11), pages R93 - R96, XP000925940
PALMER R.H. ET AL.: "Expression, purification and characterization of the ubiquitous protein kinase C-related kinase 1.", BIOCHEMICAL JOURNAL, vol. 309, no. 1, 1 July 1995 (1995-07-01), pages 315 - 320, XP000925935
BALENDRAN A. ET AL.: "PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus", CURRENT BIOLOGY, vol. 9, no. 8, 22 April 1999 (1999-04-22), pages 393 - 404, XP000925908
VANHAESEBROECK B. ET AL.: "The PI3K-PDK1 connection: more than just a road to PKB", BIOCHEMICAL JOURNAL, vol. 346, no. 3, 15 March 2000 (2000-03-15), pages 561 - 576, XP000925911
BIONDI R.M. ET AL.: "Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA", THE EMBO JOURNAL, vol. 19, no. 5, 1 March 2000 (2000-03-01), pages 979 - 988, XP002147844
BELHAM C. ET AL.: "Intracellular signalling: PDK1--a kinase at the hub of things", CURRENT BIOLOGY, vol. 9, no. 3, 11 February 1999 (1999-02-11), pages R93 - R96, XP000925940
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