PAKs, RAC/CDC42 (p21)-activated Kinases

This book covers a variety of cutting-edge basic and clinical PAK research ranging from laboratory benches to hospital beds. The goal of this book is to inspire not only biomedical research scientists and university students, but also a variety of patients who suffer from PAK-dependent diseases and clinical doctors who try to cure or delay these PAK-dependent diseases.

This book consists of 9 chapters which deal with different aspects of this kinase. These chapters are written by more than two dozen world-leading PAK experts. Each of these will provide updated biomedical information as well as future insight to a wide range of readers who are interested in this unique kinase and both its pathological and physiological roles as well as its functional evolution from its ancestral origins.

• This publication will be the very first book ever published solely focused on PAK family kinases.
• Each chapter deals with the latest progress in PAK research written by a leading PAK expert with his or her own ideas and insight.  
• Each chapter of this book has been written in such a way that clinical doctors who seek the effective cure of these formidable diseases, in addition to research scientists and biomedical students will value this book.
• This book describes in detail a number of PAK blockers which would be potentially useful for the therapy of these PAK-dependent diseases, and some of them are indeed available on the market inexpensively, without any side effect.

This book will be of interest to pharmaceutical scientists and other biomedical research scientists, clinical doctors and even patients who suffer from PAK-dependent diseases.

List of Contributors

Introduction: Pushing the Boundary Toward Clinical Application: After 35 Years, PAK Research Comes of Age

Acknowledgments

References

1. Functional Maturation of PAKs from Unicellular to Multicellular Organisms

Abbreviations

1.1 Introduction

1.2 MIHCKs/PAKs and Myosin I in Unicellular Acanthamoeba and Multicellular Dictyostelium

1.3 PAK Evolution Among Metazoans (Unicellular Versus Multicellular)

1.4 PIX in Fruit Fly Drosophila and Nematode C. elegans

1.5 FYN/ETK-Dependent Activation of PAK1

1.6 Evolution of Merlin, Nischarin, and LBK1 (PAK Inhibitors)

1.7 Concluding Remarks

Acknowledgment

References

2. Oncogenicity of PAKs and Their Substrates

Abbreviations

2.1 Introduction

2.2 Loss of Contact Inhibition of Growth

2.3 Serum-Independent Growth

2.4 Anchorage-Independent Growth

2.5 Tumor-Induced Angiogenesis

2.6 Metastasis/Invasion

2.7 PAK1/PAK4-Dependent Solid Tumors

2.8 Oncogenic Targets of PAKs

2.9 Concluding Remarks

Acknowledgments

References

3. Natural or Synthetic Therapeutics That Block PAKs

Abbreviations

3.1 Introduction

3.2 Synthetic Chemical Therapeutics

3.3 Natural PAK1 Blockers

3.4 PAK1 Blockers = AMPK Activators

Acknowledgments

References

4. PAK1–3 in Infectious Diseases

4.1 Malaria Infection

4.2 Enterobacterial Infection

4.3 Viral Infection

Acknowledgments

References

5. PAK1 in Brain Diseases or Disorders

Abbreviations

5.1 Introduction

5.2 Tumorigenesis: NF, TSC, Retinoblastoma, and Gliomas

5.3 Epilepsy

5.4 Mental Retardation

5.5 Schizophrenia

5.6 Depression

References

6. PAK1 in Alzheimer’s and Huntington’s Diseases

Abbreviations

6.1 Alzheimer’s Disease

6.2 Huntington’s Disease

Acknowledgments

References

7. PAK1 Controls the Lifespan

Abbreviations

7.1 Introduction

7.2 Snell Dwarf Mice

7.3 RAC-Deficient Drosophila

7.4 PAK1 Blockers Extend the Lifespan of Tiny Animals

7.5 Crosstalk Between PI-3 kinase-PAK1 and TOR-S6K Signaling Pathways

7.6 The Nematode Caenorhabditis japonica as a Quicker Animal Model for Elixir Screening

7.7 Antiaging (Methuselah) Venture

Acknowledgments

References

8. 3D Structure and Physiological Regulation of PAKs

8.1 The PAK Family of Protein Kinases

8.2 Structural Mechanisms of PAK Regulation

8.3 Alternative Mechanisms Leading to PAK Activation

8.4 PAK Substrate Specificity and Downstream Signaling Events

Acknowledgments

References

Epilogue: “Lateral Thinking” Is the Key to a Great Leap in Biomedical Sciences

References

About the Authors