Kinomics : approaches and applications / edited by Heinz-Bernhard Kraatz and Sanela Martic. -- Weinheim [Germany] : Wiley-VCH, c2015. – (58.174354/K55)

Contents

List of Contributors  XIII

Preface  XIX

Part I      Protein Kinases Cell Signaling  1

1  Global Approaches to Understanding Protein Kinase Functions

1.1  A Brief History of the Structure of the Human Kinome  3

1.2  Why Study Protein Kinases - Their Roles in Disease  10

1.3  Methodology for Assessment of Protein Kinase Functions  16

1.4  Final Thoughts  28

Acknowledgments  29

References  29

2  "Genuine" Casein Kinase (Fam20C): The Mother of the Phosphosecretome  47

2.1  Introduction  47

2.2  Early Detection of the pS-x-E Motif in Secreted Phosphoproteins  48

2.3  CK1 and CK2 are Not Genuine Casein Kinases  50

2.4  Polo-Like Kinases: Newcomers in the Club of False "Casein Kinases"  51

2.5  Characterization of an Orphan Enzyme: The Spectacular Performance ofa Peptide Substrate  51

2.6  Catalytic Activity of Fam20C: Mechanistic Aspects  53

2.7  A Kinase in Need of Control  54

2.8  Outlook  57

Funding  58

References  58

3  Chemical Biology of Protein Kinases  63

3.1  The Basis of Chemical Genetics  63

3.2  Protein Kinase ChemicalGenetics  65

3.3  Applications for AS Kinases  68

3.4  Current Challenges  77

3.5  Conclusions  80

Acknowledgments  81

References  81

4  Protein Kinases and Caspases: Bidirectional Interactions in Apoptosis  85

4.1  Introduction  85

4.2  Apoptosis: Caspase-Dependent Pathways  86

4.3  Functional Crosstalk between Protein Kinases and Caspases  88

4.4  Strategies to Investigate Global Crosstalk between Protein Kinases and Caspases  99

4.5  Implications and Future Prospects  103

References  104

5  The Kinomics of Malaria  115

5.1  Introduction  115

5.2  The Plasmodium Kinome: Salient Features  117

5.3  Reverse Genetics of the Plasmodium Kinome  120

5.4  Lessons from Phosphoproteomics  123

5.5  Host Cell Kinomics in Malaria Infection  127

5.6  Targeting Protein Kinases in Antimalarial Drug Discovery  128

5.7  Concluding Remarks  130

References  130

Part II      ATPCo-substrateDesign  137

6  ATP Analogs in Protein Kinase Research  139

6.1  Base-Modified ATP Analogs  140

6.2  Sugar-Modified ATP Analogs  148

6.3  a- and [3-Phosphate-Modified ATP Analogs  149

6.4  γ-Phosphate-Modified ATP Analogs  152

6.5  Conclusions  161

References  163

7  Electrochemical Detection of Protein Kinase-Catalyzed Phosphorylations  169

7.1  Introduction  169

7.2  Conclusions  187

References  190

Part III     New Methodologies for Kinomics  193

8  Phos-tag Technology for Kinomics  195

8.1  Introduction  195

8.2  Kinomics and Phosphoproteomics  196

8.3  Phos-tag Technology  196

8.4  Highly Sensitive Detection of Phosphopeptides and Phosphoproteins bythe Phos-tag Biotin Method  197

8.5  Protein Kinase Assay with Phos-tag Sodium Dodecyl Sulfate-Polyacrylamide GelElectrophoresis  201

8.6  Conclusion  208

References  208

9  Development of Species- and Process-Specific Peptide Kinome Arrays with Priority Application to Investigations of Infectious Disease  211

9.1  Phosphorylation-Mediated Signal Transduction  211

9.2  Peptide Arrays for Kinome Analysis  213

9.3  Infectious Disease  218

9.4  Conclusions  228

References  229

10  New Approaches to Understanding Bacterial Histidine Kinase Activity and Inhibition  233

10.1  Introduction to Two-Component System Signaling  233

10.2  Focus on Bacterial HKs  235

10.3  Bacterial HK Activity  235

10.4  Bacterial HK Inhibition  242

10.5  Outlook on Tools for the Study and Inhibition of Bacterial HKs  248

References  248

11  Methods for Large-Scale Identification of Protein Kinase Substrate Networks

11.1  Introduction  255

11.2  Computational Prediction of Phosphorylation Sites and Protein Kinase-Substrate Relationships  256

11.3  The Role of Mass Spectrometry in Identifying Posttranslational Modifications

11.4  Analog-Sensitive Kinases and Other Specific Inhibitors  264

11.5  Array-Based Methods  266

11.6  Solution-Based Methods  269

11.7  Future Perspectives  271

References  272

Part IV     Kinaselnhibition  281

12  Developing Inhibitors of STAT3: Targeting Downstream of the Kinases for Treating Disease  283

12.1  Introduction  283

12.2  STAT3 Structure and Signaling  284

12.3  Methods for Directly Inhibiting STAT3  288

12.4  Conclusion  296

References  298

13  Metal Compounds as Kinase and Phosphatase Inhibitors in Drug Development: The Role of the Metal and Ligands  301

13.1  Introduction  301

13.2  Kinase Inhibitors: From Ideal 3D Shapes to Kinase Inhibitor-Derived Ligands in Metal Complexes  302

13.3  Phosphatases and Metal Compounds  319

13.4  Conclusions  323

Acknowledgments  323

References  324

Index  331