PAKs, RAC/CDC42 (p21)-activated Kinases

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