Hedgehog Signaling

Hedgehog Signaling

1st Edition - March 2, 2012

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  • Editor: Gerald Litwack
  • Hardcover ISBN: 9780123946225
  • eBook ISBN: 9780123948380

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First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on hedgehog signaling.

Key Features

  • Contributions from leading authorities
  • Informs and updates on all the latest developments in the field


Researchers, faculty, and graduate students interested in cutting-edge review concerning the molecular and cellular biology of vitamins, hormones, and related factors and co-factors. Libraries and laboratories at institutes with strong programs in cell biology, biochemistry, molecular biology, gene regulation, hormone control, and signal transduction are likely to be interested

Table of Contents

  • Former Editors



    Chapter One: Hedgehog Signaling

    I. Hedgehog Ligands

    II. Hedgehog Signaling

    III. Hedgehog Signaling in Zebrafish Eye Vesicle Patterning

    IV. Hedgehog Signaling in Zebrafish Photoreceptor Differentiation

    V. Hedgehog Signaling in Zebrafish Inner Nuclear Layer

    VI. Hedgehog Signaling in Zebrafish Ganglion Cell Differentiation

    Chapter two: Canonical and Noncanonical Hedgehog/GLI Signaling in Hematological Malignancies

    I. Hedgehog Introduction

    II. Regulation of Canonical HH Signaling and Its Implication in Cancer

    III. SMO-Independent Modulation of GLI Activity

    IV. Hedgehog in Hematopoiesis and Hematopoietic Stem Cells

    V. From HSC to CML

    VI. T- and B-Cell Malignancies

    VII. Outlook

    Chapter three: Noncanonical Hedgehog Signaling

    I. Definition

    II. Type I Noncanonical Signaling: Pathways Engaged Exclusively by Ptc1

    III. Type II Noncanonical Signaling: Pathways Engaged by Smoothened

    IV. Noncanonical Hh Signaling in Drosophila

    V. Concluding Remarks

    Chapter four: Gli Protein Nuclear Localization Signal

    I. Introduction

    II. Nuclear Localization Signal and Nuclear Export Signal

    III. NLS and NES Mapping

    IV. Sequence Comparison of Gli NLSs—NLSs in ZF Domains

    V. Predicted 3D Structure of Gli NLS

    VI. NLS Control of Gli/Ci Subcellular Localization in Hh Signaling

    VII. Perspectives

    Chapter five: Mammalian Homologues of Drosophila Fused Kinase

    I. Introduction

    II. The Major Steps of Hh Signaling

    III. Ci/Gli Proteins are Transcription Factors Mediating Hh Activities

    IV. Hedgehog Signaling Complex is Responsible for Regulation of ci Protein

    V. Regulation of Gli Proteins

    VI. Fu is a Protein Kinase Playing Catalytic and Regulatory Roles in ci regulation

    VII. Protein Kinases Participating in the Regulation of Gli Proteins

    VIII. Controversial Roles of Stk36

    IX. The Role of Ulk3 in Shh Signaling Pathway

    X. An Emerging Shh Signaling Model Involving Ulk3

    Chapter six: Identification, Functional Characterization, and Pathobiological Significance of GLI1 Isoforms in Human Cancers

    I. Introduction

    II. Structures and Properties of GLI1 Isoforms

    III. Regulation of GLI1 Isoforms by Canonical and Noncanonical Pathways

    IV. GLI1 Isoforms and Malignant Phenotypes of Cancer

    V. Conclusion and Future Directions

    Chapter seven: Gli-Similar Proteins

    I. Introduction

    II. Mechanism of Action of Glis Proteins

    III. Role of Glis Proteins in Renal Physiology and Pathology

    IV. Role of Glis3 in Pancreas Physiology and Pathology

    V. Glis Functions in Other Tissues

    VI. Conclusion

    Chapter eight: Sonic Hedgehog Regulates Wnt Activity During Neural Circuit Formation

    I. Introduction

    II. Shh and Wnt Signaling: Canonical Signaling Pathways

    III. Patterning and Morphogenesis of the Neural Tube

    IV. Establishment of Neuronal Polarization

    V. Axon Guidance

    VI. Synapse Formation

    VII. Other Factors Influencing Shh and Wnt Pathways

    VIII. Conclusions and Future Directions

    Chapter nine: Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay

    I. Introduction

    II. Ubiquitin-Dependent Regulation of Hh Signaling

    III. Increasing the Complexity of Hh Signaling in Vertebrates: The Cul1- and Cul3-Dependent Ubiquitination Processes

    IV. An Alternative Gli1 Control by the HECT-Type Itch E3 Ubiquitin Ligase-Based Processing

    V. Activation of Itch Function by Numb

    VI. Acetylation to Ubiquitination Connection in Hh Signaling

    VII. Implications of Ubiquitin-Dependent Events for Cell Development and Tumorigenesis

    VIII. Implications for Ubiquitination/Acetylation Interplay in Cell Development and Cancer Control

    IX. Conclusions

    Chapter ten: Palmitoylation of Hedgehog Proteins

    I. Introduction to Protein Palmitoylation

    II. Palmitoylation of Hedgehog Proteins

    III. Palmitoylation of Other Secreted Proteins

    IV. The MBOAT Family of Acyltransferases

    V. Conclusions and Future Directions

    Chapter eleven: Phosphorylation Regulation of Hedgehog Signaling

    I. Introduction

    II. Phosphorylation of the Transcription Factor in Hh Signaling

    III. Phosphorylation of Smo Receptor in Hh Signaling

    IV. Other Phosphorylation Events in Hh Signaling

    V. Nonconserved Phosphorylation

    VI. Phosphatases in Hh Signaling

    VII. Differential Phosphorylation of Hh Signaling Components

    Chapter twelve: Protein Kinase A Activity and Hedgehog Signaling Pathway

    I. Introduction

    II. Function of PKA in Hedgehog-Responsive Cells

    III. Activation of PKA

    IV. PKA Activity in Hedgehog-Responding Cells

    V. Perspectives

    Chapter thirteen: Phosphorylation of Gli by cAMP-Dependent Protein Kinase

    I. Introduction

    II. cAMP-Dependent Protein Kinase

    III. Hedgehog Signaling and cAMP-Dependent Protein Kinase

    IV. Gli Transcription Factors and cAMP-Dependent Protein Kinase

    V. Conclusions

    Chapter fourteen: ZFP932 Suppresses Cellular Hedgehog Response and Patched1 Transcription

    I. Introduction

    II. Zfp932 Characterization

    III. ZFP932 Represses Ptch1 Expression

    IV. ZFP932 Represses Cellular Hedgehog-Signaling Response

    V. ZFP932 Regulates Osteoblast Differentiation

    VI. Conclusion

    Chapter fifteen: A New Era for an Ancient Drug

    I. Historic Use of Arsenic in Medicine

    II. Molecular Mechanisms of Arsenic in Cancer Therapy

    III. Role of Hedgehog Signaling in Cancer

    IV. Effect of Arsenic on Hh Signaling

    V. Conclusions

    Chapter sixteen: Aberrations and Therapeutics Involving the Developmental Pathway Hedgehog in Pancreatic cancer

    I. Introduction

    II. The Hedgehog Pathway

    III. Hedgehog Therapeutics

    IV. Conclusion

    Chapter seventeen: Sonic Hedgehog Signaling and Potential Therapeutic Indications

    I. Sonic Hedgehog Discovered (Shh)

    II. Shh Signaling in Vertebrates

    III. Shh Second Messenger Systems

    IV. Shh in Stem Cell Proliferation

    V. Shh in Oncogenesis

    VI. Shh in Injury of the CNS

    VII. Conclusion

    Chapter eighteen: Sonic Hedgehog on Microparticles and Neovascularization

    I. Introduction

    II. Neovascularization

    III. Sonic Hedgehog

    IV. Microparticles

    V. Conclusion

    Chapter nineteen: “Patch”-ing up the Neurons

    I. Introduction

    II. The “Patched” Transmission

    III. Ptch1 Expression in Neural Tissues

    IV. Ptch1 in Disease, Development, and Injury

    V. Conclusion

    Chapter twenty: Activation of Hedgehog Pathway in Gastrointestinal Cancers

    I. Introduction

    II. Activation of the Hh Pathway in Esophageal Cancer

    III. Activation of the Hh Pathway in Gastric Cancer

    IV. Activation of the Hh Pathway in Colorectal Cancer

    V. Summary

    Chapter twenty-one: The Role of Sonic Hedgehog as a Regulator of Gastric Function and Differentiation

    I. Introduction

    II. Hh in the Adult Stomach

    III. The Potential Role of Sonic Hh as a Gastric Hormone

    IV. Conclusions and Future Directions

    Chapter twenty-two: Sonic Hedgehog-Mediated Synergistic Effects Guiding Angiogenesis and Osteogenesis

    I. General Introduction

    II. General Aspects of Shh Signaling

    III. The Role of Hh Morphogens in Bone Development and Repair

    IV. Shh: Potential Candidate Linking Angiogenesis and Osteogenesis

    V. Effects of Shh on Angiogenesis, Vessel Maturation, and Osteogenesis

    VI. Coculture Models as In Vitro Models to Investigate Effects of Shh on Osteogenesis and Angiogenesis

    VII. Effects of Shh on Angiogenesis in a Coculture Model

    VIII. Effects of Shh on Osteogenesis in a Coculture Model

    IX. Future Therapeutical Options and Delivery Strategies

    Chapter twenty-three: Hedgehog Inhibition as an Anti-Cancer Strategy

    I. Introduction

    II. Hh Signaling in Normal Development

    III. Hh Pathway Alterations in Cancer

    IV. Targeted Therapies for Hedgehog Dependent Cancers

    V. Conclusions and Future Directions


Product details

  • No. of pages: 584
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: March 2, 2012
  • Imprint: Academic Press
  • Hardcover ISBN: 9780123946225
  • eBook ISBN: 9780123948380

About the Serial Editor

Gerald Litwack

Gerald Litwack
Dr. Gerald Litwack obtained M.S. and PhD degrees from the University of Wisconsin Department of Biochemistry and remained there for a brief time as a Lecturer on Enzymes. Then he entered the Biochemical Institute of the Sorbonne as a Fellow of the National Foundation for Infantile Paralysis. He next moved to Rutgers University as an Assistant Professor of Biochemistry and later as Associate Professor of biochemistry at the University of Pennsylvania Graduate School of Medicine. After four years he moved to the Temple University School of Medicine as Professor of Biochemistry and Deputy Director of the Fels Institute for Cancer Research and Molecular Biology, soon after, becoming the Laura H. Carnell Professor. Subsequently he was appointed chair of Biochemistry and Molecular Pharmacology at the Jefferson Medical College as well as Vice Dean for Research and Deputy Director of the Jefferson Cancer Institute and Director of the Institute for Apoptosis. Following the move of his family, he became a Visiting Scholar at the Department of Biological Chemistry of the Geffen School of Medicine at UCLA and then became the Founding Chair of the Department of Basic Sciences at the Geisinger Commonwealth School of Medicine, becoming Professor of Molecular and Cellular Medicine and Associate Director of the Institute for Regenerative Medicine at the Texas A&M Health Science Center as his final position. During his career he was a visiting scientist at the University of California, San Francisco and Berkeley, Courtauld Institute of Biochemistry, London and the Wistar Institute. He was appointed Emeritus Professor and/or Chair at Rutgers University, Thomas Jefferson University and the Geisinger Commonwealth School of Medicine. He has published more than 300 scientific papers, authored three textbooks and edited more than sixty-five books. Currently he lives with his family and continues his authorship and editorial work in Los Angeles.

Affiliations and Expertise

Emeritus Professor and/or Chair at Rutgers University, Thomas Jefferson University and the Geisinger Commonwealth School of Medicine, USA; Toluca Lake, North Hollywood, California, USA

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