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Preface; About the Editors; Contents; Chapter 1: The Eukaryotic Protein Kinase Superfamily and the Emergence of Receptor Tyrosine Kinases; 1.1 The Human Kinome; 1.2 Protein Kinases and Human Disease; 1.3 Kinome Evolution; 1.4 The Genesis of Receptor Tyrosine Kinases; 1.5 Evolution of the Receptor Tyrosine Kinases; 1.6 The Development of Ligand-Regulated RTK Activity; 1.7 Coda; References; Chapter 2: Evolution of Receptor Tyrosine Kinases; 2.1 Introduction; 2.2 The EGF Receptor Family; 2.3 The Insulin Receptor Family; 2.4 The FGF Receptor Family; 2.5 The VEGF Receptor Family
2.6 The PDGF Receptor Family2.7 The NTRK Family; 2.8 The TAM Receptor Family; 2.9 The DDR Family; 2.10 The EPH Receptor Family; 2.11 The ROR, TIE, MET, and ALK Receptor Families; 2.12 MUSK, PTK7, RET, ROS, and RYK; 2.13 The NOK Family; 2.14 Evolution of RTK Ligands; 2.15 EGFR Ligands; 2.16 The FGF Family; 2.17 The PDGF/VEGF Family of Growth Factors; 2.18 Conclusions; References; Chapter 3: RTKs in Invertebrates: Lessons in Signal Transduction; 3.1 Families of RTKs in Drosophila; 3.2 Linear vs. Branched RTK Signaling Pathways; 3.3 Spatial and Temporal Features of RTK Signaling
3.4 Restricting the Range of RTK Signaling3.5 Concept of "Ratchet-Like" Signal Expansion; 3.6 Integral vs. Auxiliary Elements in the Signaling Pathway of RTKs; 3.7 Cell Biology of RTK Signaling During Development; 3.8 Transcriptional Output of RTK Pathways; 3.9 Overlap Between RTKs and Other Signaling Pathways; References; Chapter 4: Receptor Tyrosine Kinase Signal Transduction and the Molecular Basis of Signalling Specificity; 4.1 Introduction; 4.2 RTKs Assemble into Dimeric Allosteric Enzymes; 4.3 Cooperative Interactions in Ligand Binding to RTKs and Other Surface Receptors
4.4 Allosteric Activation of RTKs Intracellular Kinase Domains4.5 RTK Intracellular Signalling Pathways; 4.6 The Paradox of Signalling Specificity; 4.7 Systems Biology of Combinatorial Signalling; 4.8 Cell Cycle Regulation by RTKs; 4.9 Regulation of Apoptosis by RTKs; 4.10 Conclusion and Perspectives; References; Chapter 5: Nuclear Functions of Receptor Tyrosine Kinases; 5.1 Introduction; 5.2 EGFR Family; 5.2.1 Discovery of Nuclear EGFR Family; 5.3 Functions of EGFR Family in the Nucleus; 5.3.1 EGFR/ErbB-1; 5.3.2 ErbB-2/HER-2; 5.3.3 ErbB-3; 5.3.4 ErbB-4; 5.4 FGFR Family; 5.4.1 FGFR1
5.4.2 FGFR25.4.3 FGFR3 and FGFR4; 5.5 VEGFR Family; 5.5.1 VEGFR-1; 5.5.2 VEGFR-2; 5.6 Other Receptor Tyrosine Kinases; 5.6.1 Insulin Receptor Family; 5.6.1.1 Insulin Receptor; 5.6.1.2 Insulin-Like Growth Factor I Receptor; 5.6.2 HGF Receptor Family; 5.6.3 ROR; 5.6.4 Eph Receptors; 5.6.5 Ryk; 5.6.6 Trk; 5.6.7 Mer; 5.6.8 PDGFR-Alpha; 5.7 Summary; 5.8 Conclusion; References; Chapter 6: Computational and Modeling Aspects of RTK Networks; 6.1 Introduction; 6.2 Topic 1: The Multilayered ERBB Signaling Network; 6.2.1 The Input Layer; 6.2.1.1 Combinatorial Complexity of the Input Layer
2.6 The PDGF Receptor Family2.7 The NTRK Family; 2.8 The TAM Receptor Family; 2.9 The DDR Family; 2.10 The EPH Receptor Family; 2.11 The ROR, TIE, MET, and ALK Receptor Families; 2.12 MUSK, PTK7, RET, ROS, and RYK; 2.13 The NOK Family; 2.14 Evolution of RTK Ligands; 2.15 EGFR Ligands; 2.16 The FGF Family; 2.17 The PDGF/VEGF Family of Growth Factors; 2.18 Conclusions; References; Chapter 3: RTKs in Invertebrates: Lessons in Signal Transduction; 3.1 Families of RTKs in Drosophila; 3.2 Linear vs. Branched RTK Signaling Pathways; 3.3 Spatial and Temporal Features of RTK Signaling
3.4 Restricting the Range of RTK Signaling3.5 Concept of "Ratchet-Like" Signal Expansion; 3.6 Integral vs. Auxiliary Elements in the Signaling Pathway of RTKs; 3.7 Cell Biology of RTK Signaling During Development; 3.8 Transcriptional Output of RTK Pathways; 3.9 Overlap Between RTKs and Other Signaling Pathways; References; Chapter 4: Receptor Tyrosine Kinase Signal Transduction and the Molecular Basis of Signalling Specificity; 4.1 Introduction; 4.2 RTKs Assemble into Dimeric Allosteric Enzymes; 4.3 Cooperative Interactions in Ligand Binding to RTKs and Other Surface Receptors
4.4 Allosteric Activation of RTKs Intracellular Kinase Domains4.5 RTK Intracellular Signalling Pathways; 4.6 The Paradox of Signalling Specificity; 4.7 Systems Biology of Combinatorial Signalling; 4.8 Cell Cycle Regulation by RTKs; 4.9 Regulation of Apoptosis by RTKs; 4.10 Conclusion and Perspectives; References; Chapter 5: Nuclear Functions of Receptor Tyrosine Kinases; 5.1 Introduction; 5.2 EGFR Family; 5.2.1 Discovery of Nuclear EGFR Family; 5.3 Functions of EGFR Family in the Nucleus; 5.3.1 EGFR/ErbB-1; 5.3.2 ErbB-2/HER-2; 5.3.3 ErbB-3; 5.3.4 ErbB-4; 5.4 FGFR Family; 5.4.1 FGFR1
5.4.2 FGFR25.4.3 FGFR3 and FGFR4; 5.5 VEGFR Family; 5.5.1 VEGFR-1; 5.5.2 VEGFR-2; 5.6 Other Receptor Tyrosine Kinases; 5.6.1 Insulin Receptor Family; 5.6.1.1 Insulin Receptor; 5.6.1.2 Insulin-Like Growth Factor I Receptor; 5.6.2 HGF Receptor Family; 5.6.3 ROR; 5.6.4 Eph Receptors; 5.6.5 Ryk; 5.6.6 Trk; 5.6.7 Mer; 5.6.8 PDGFR-Alpha; 5.7 Summary; 5.8 Conclusion; References; Chapter 6: Computational and Modeling Aspects of RTK Networks; 6.1 Introduction; 6.2 Topic 1: The Multilayered ERBB Signaling Network; 6.2.1 The Input Layer; 6.2.1.1 Combinatorial Complexity of the Input Layer