Biochemistry of signal transduction and regulation:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Weinheim
Wiley-VCH
2008
|
| Ausgabe: | 4. enlarged and improved ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XX, 626 S. Ill., graph. Darst. |
| ISBN: | 9783527313976 |
Internformat
MARC
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| 100 | 1 | |a Krauss, Gerhard |d 1943- |e Verfasser |0 (DE-588)133839915 |4 aut | |
| 245 | 1 | 0 | |a Biochemistry of signal transduction and regulation |c Gerhard Krauss |
| 250 | |a 4. enlarged and improved ed. | ||
| 264 | 1 | |a Weinheim |b Wiley-VCH |c 2008 | |
| 300 | |a XX, 626 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 0 | 7 | |a Regulation |0 (DE-588)4049075-0 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Molekularbiologie |0 (DE-588)4039983-7 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Signaltransduktion |0 (DE-588)4318717-1 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4123623-3 |a Lehrbuch |2 gnd-content | |
| 689 | 0 | 0 | |a Signaltransduktion |0 (DE-588)4318717-1 |D s |
| 689 | 0 | 1 | |a Regulation |0 (DE-588)4049075-0 |D s |
| 689 | 0 | 2 | |a Molekularbiologie |0 (DE-588)4039983-7 |D s |
| 689 | 0 | |8 1\p |5 DE-604 | |
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| 999 | |a oai:aleph.bib-bvb.de:BVB01-015989147 | ||
| 883 | 1 | |8 1\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
Datensatz im Suchindex
| _version_ | 1804137046288105472 |
|---|---|
| adam_text | IX
Contents
Preface VII
1
Basics of Cell Signaling
1
1.1
Cell Signaling: Why, When and Where?
1
1.2
Intercellular Signaling
3
1.2.1
Tools for Intercellular Signaling
3
1.2.2
Steps of Intercellular Signaling
S
1.2.3
Regulation of Intercellular Signaling
7
1.3
Hormones in Intercellular Signaling
8
1.3.1
Chemical Nature of Hormones
8
1.3.2
Hormone Analogs: Agonists and Antagonists
12
1.3.3
Endocrine, Paracrine and
Autocrine
Signaling
13
1.3.4
Direct Protein Modification by Signaling Molecules
25
1.4
Intracellular Signaling: Basics
í
5
1.4.1
Reception of External Signals IS
1.4.2
Activation and Deactivation of Signaling Proteins ?6
1.4.3
Processing of Multiple Signals
17
1.4.4
Variability of Signaling Proteins
17
1.5
Molecular Tools for Intracellular Signaling
18
1.5.1
Receptors
18
1.5.2
Signaling Enzymes
21
1.5.3
Adaptors and Scaffolding Proteins
22
1.5.4
Diffusible Intracellular Messengers: Second Messengers
22
1.6
Basic Mechanisms of Intracellular Signaling
24
1.6.1
Regulatory Modifications
24
1.6.2
Recognition of Protein Modifications by
Modification-specific Protein Modules
25
1.6.3
Multisite Protein Modification
26
1.6.4
Protein Interaction Domains
28
1.7
Modular Structure of Signaling Proteins and
Signaling Complexes
32
1.7.1
Modules in Signaling Proteins
32
1.7.2
Modular Signaling Complexes
33
Χ ι
Contents
1.8
Organization of Signaling
34
1.8.1
Linear Signaling Pathways, Branching and Crosstalk
35
1.8.1.1
Linear Pathways
35
1.8.1.2
Branching and Crosstalk
37
1.8.1.3
Interactions between Signaling Paths
37
1.8.2
Signaling Networks
38
1.8.2.1
Complexity of Signaling Networks
39
1.8.2.2
Properties of Signaling Networks
39
1.8.2.3
Nodes and Junctions
41
1.8.2.4
Feedback Loops
42
1.8.3
Redundancy and Specificity of Signaling
46
1.8.4
Regulation of Signaling Pathways
47
1.8.5
Spatial Organization of Signaling Pathways
49
1.8.6
Compartmentalization and Transport
50
1.8.7
Evolution of Signaling Pathways
51
1.9
Variability and Cell-type Specificity of Signaling
51
1.10
References
53
2
Regulation of Enzyme Activity
55
2.1
Basis of Enzyme Catalysis
56
2.2
Basics of Allosteric Regulation
58
2.3
Regulation of Enzymes by Effector Molecules
60
2.4
Regulation of Enzyme Activity by Phosphorylation
62
2.5
Ubiquitin
(Ub)-Proteasome
Pathway
64
2.5.1
Components of the Ub System
65
2.5.2
Ub and Ub-like Proteins
66
2.5.3
Activation and Transacylation of Ub:
El and E2 Enzymes
67
2.5.4
Transfer to the Target Protein with the Participation
of E3
69
2.5.5
HECT Domain E3 Enzymes
71
2.5.6
RING Domain E3 Enzymes
72
2.5.6.1
N-end Rule Enzymes
73
2.5.6.2
Cbl Protein
73
2.5.6.3
Cullin-based E3 Enzymes, SCF and APC
74
2.5.6.4
Processing of Nuclear Factor
(NF) kB
and Degradation
of IkB
76
2.5.7
Degradation in the Proteasome
78
2.5.8
Other Regulatory Functions of Ub Conjugation
80
2.5.9
Regulation of Proteins by Sumoylation
82
2.6
Lipidation of Signaling Proteins
83
2.6.1
Myristoylation
84
2.6.2
Palmitoylarion
85
2.6.3
Farnesylation and Geranylation
86
2.6.4
Dual Lipidation
87
Contents
XI
2.6.5
Cholesterol
Membrane
Anchor
88
2.6.6 Switch
Function of
Lipid
Anchors
88
2.6.7
Glycosylphosphatidylinositol (GPI) Anchor
90
2.7
References
91
3
Regulation of Gene Expression
93
3.1
Basic Steps of Gene Expression
93
3.2
Components of the Eukaryotic Transcription Machinery
95
3.2.1
Basic Features of Eukaryotic Transcription
96
3.2.2
Elementary Steps of Eukaryotic Transcription
98
3.2.3
Eukaryotic
RNA Polymerases
98
3.2.4
Structure of the Transcription Start Site and
Regulatory Sequences
100
3.2.5
General Transcription Factors and the
Core Transcription Apparatus
101
3.2.6
Holoenzyme Forms of
RNA
Pol II
103
3.2.7
Phosphorylation of
RNA Pol
II and the Onset
of Transcription
204
3.2.8
TFIIH
-
A Pivotal Regulatory Protein Complex
106
3.2.9
Mediator Complex
107
3.3
Principles of Transcription Regulation
109
3.3.1
Elements of Transcription Regulation
109
3.3.2
Regulation of Eukaryotic Transcription by Sequence-specific
DNA-binding Proteins 111
3.3.3 DNA
Binding of Transcriptional Regulators
112
3.3.4
Structure of the Recognition Sequence and Quaternary
Structure of DNA-binding Proteins
113
3.3.5
Communication with the Transcription Apparatus:
Transactivation Domains
115
3.3.6
Families of Sequence-specific Transcription Factors and
Homo- or Heterodimerization
126
3.4
Control of Transcription Factors
118
3.4.1
Mechanisms for the Control of Regulatory DNA-binding
Proteins
278
3.4.2
Changes in the Concentration of Regulatory DNA-binding
Proteins
119
3.4.3
Regulation by Binding of Effector Molecules
329
3.4.4
Posttranslational Modification of Transcription
Regulators
220
3.4.5
Regulation by Phosphorylation
221
3.4.6
Regulation by Methylation, Acetylation and
Redox
Modification
225
XII Contents
3.4.7 Transcriptional Regulation in
the
Framework
of
Signal Transduction Networks 125
3.4.7.1 Constitutively Active
Transcription Factors
126
3.4.7.2
Regulatory Transcription Factors
126
3.4.8
Repression of Transcription
128
3.4.9
Coregulators of Transcription
130
3.5
Chromatin Structure and Transcription Regulation
131
3.5.1
Nucleosome and Chromatin Structure
132
3.5.2
Histone Acetylation and Deacetylation
134
3.5.3
Histone Methylation
136
3.5.3.1
Histone
Arginine
Methylation
136
3.5.3.2
Arginine Demethylation/Citrullination
138
3.5.3.3
Histone
Lysine
Methylation
138
3.5.3.4
Histone
Lysine
Demethylation
139
3.5.4
Histone Phosphorylation
140
3.5.5
Histone Ubiquitination and Sumoylation
141
3.5.6
Histone Modification Code
141
3.5.7
Recognition of Histone Modifications by
Protein Domains
143
3.5.8 DNA
Methylation
144
3.5.9
Summary of the Regulatory Steps in Transcription
148
3.6
Posttranscriptional Regulation of Gene Expression
150
3.6.1
Control at the Level of Pre-mRNA Processing
351
3.6.2
Stability of mRNA
155
3.6.3
Regulation at the Level of Translation
157
3.6.3.1
General Mechanisms of Translational Control
157
3.6.3.2
mRNA-specific Regulation by
5
Sequences:
Control of Ferritin mRNA Translation by Iron
159
3.6.3.3
mRNA-specific Translational Regulation by
Protein Binding to
3
-Untranslated Regions
160
3.6.3.4
Global Translational Regulation of mRNAs by
Targeting
ЄІР-4Е
162
3.6.3.5
Regulation of Translation via elF-2
164
3.7
Regulation by
RNA
Interference (RNAi)
167
3.7.1
Small Regulatory RNAs
170
3.7.2
Incorporation of Small RNAs into RISC
172
3.7.3
Cleaving the Target
RNA
173
3.7.4
Specificity and Target Selection in RNAi
175
3.7.5
Biological Functions of RNAi
176
3.7.5.1
Functions and Applications of siRNAs
176
3.7.5.2
Functions of miRNAs
176
3.7.5.3
RISCs and Chromatin Structure
177
3.8
References
179
Contents
XIII
4
Signaling by Nuclear Receptors
181
4.1
Ligands of Nuclear Receptors
181
4.2
Principles of Signaling by Nuclear Receptors
184
4.3
Classification and Structure of Nuclear Receptors
186
4.3.1
DNA-binding Elements of Nuclear Receptors: HREs
187
4.3.2
The DNA-binding Domain of Nuclear Receptors
189
4.3.3
HRE
Recognition and Structure of the HRE-Receptor
Complex
190
4.3.4
Ligand-binding Domain (LBD)
191
4.3.5
Transactivating Elements of the Nuclear Receptors
195
4.4
Mechanisms of Transcriptional Regulation by
Nuclear Receptors
196
4.4.1
Steroid Receptor Coactivator (SRC)-l/pl60 and
Thyroid Hormone Receptor-activating Protein (TRAP)
Coactivators
198
4.4.2
Corepressors of Nuclear Receptors
200
4.5
Regulation of Signaling by Nuclear Receptors
200
4.6
The Signaling Pathway of the Steroid Hormone
Receptors
203
4.7
Signaling by Retinoids, Vitamin D3 and the
T3 Hormone
205
4.8
Nongenomic Functions of Nuclear Receptors and
their Ligands
207
4.9
References
211
5
G-protein-coupled Signal Transmission Pathways
213
5.1 Transmembrane (TM)
Receptors: General Structure and
Classification
213
5.2
Structural Principles of TM Receptors
215
5.2.1
The Extracellular Domain of TM Receptors
217
5.2.2
TM Domain
217
5.2.3
Intracellular Domain of Membrane Receptors
219
5.2.4
Regulation of Receptor Activity
221
5.3
GPCRs
222
5.3.1
Classification of GPCRs
223
5.3.2
Structure of GPCRs
225
5.3.3
Ligand Binding and Mechanism of
Signal Transmission
227
5.3.4
Regulation of GPCRs
228
5.3.5
Switching Off and Desensitization of 7TM Receptors
229
5.3.6
Dimerization of GPCRs
233
5.4
Regulatory GTPases
233
5.4.1
The GTPase Superfamily: General Functions and
Mechanism
234
5.4.2
Inhibition of GTPases by GTP Analogs
236
XIV Contents
5.4.3
The G-domain as a Common Structural Element of
the GTPases
237
5.4.4
GTPase Families
238
5.5
Heterotrimeric G-proteins
239
5.5.1
Classification of the Heterotrimeric G-proteins
240
5.5.2
Toxins as Tools in the Characterization of
Heterotrimeric G-proteins
243
5.5.3
Functional Cycle of Heterotrimeric G-proteins
244
5.5.4
Structural and Mechanistic Aspects of the Switch Function
of G-proteins
247
5.5.5
Structure and Function of the
βγ
-Complex
253
5.5.6
Membrane Association of the G-proteins
255
5.5.7
Regulators of G-proteins: Phosducin and RG
S
Proteins
256
5.6
Receptor-independent Functions of Heterotrimeric
G-proteins
259
5.7
Effector Molecules of G-proteins
259
5.7.1
Adenylyl Cyclase and cAMP as Second Messenger
260
5.7.2
PLC
264
5.8
GPCR Signaling via
Arrestin 26S
5.9
References
269
6
Intracellular Messenger Substances: Second Messengers
271
6.1
General Properties of Intracellular Messenger
Substances
272
6.2
cAMP
273
6.3
cGMP and Guanylyl Cyclases
275
6.3.1
Guanylyl Cyclases
276
6.3.2
Targets of cGMP
277
6.4
Metabolism of Inositol Phospholipids and
Inositol Phosphates
278
6.5
Storage and Release of Ca2+
282
6.5.1
Release of Ca2+ from Ca2+ Storage
282
6.5.2
Influx of Ca2+ from the Extracellular Region
288
6.5.3
Removal and Storage of Ca2+
288
6.5.4
Temporal and Spatial Changes in Ca2+ Concentration
289
6.6
Functions of Phosphoinositides
290
6.6.1
Messenger Function of PtdIns(3,4,5)P3
291
6.6.2
Functions of PtdIns(4,5)P2 and other
Phosphoinositides
291
6.7
Ca2+ as a Signal Molecule
292
6.7.1
Calmodulin as a Ca2+ Sensor
295
6.7.2
Target Proteins of Ca^/Calmodulin
297
6.7.3
Other Ca2+ Sensors
298
6.8
DAG as a Signal Molecule
299
6.9
Other
Lipid
Messengers
300
Contents
I XV
6.10
NO Signaling Molecule
301
6.10.1
Reactivity of NO
302
6.10.2
Synthesis of NO
303
6.10.3
Physiological Functions of Nitrosylation
305
6.10.3.1
Nitrosylation of Metal Centers
305
6.10.3.2
Regulatory Functions of
S
-Nitrosylation
307
6.10.3.3
Toxic Action of NO and Nitrosative Stress
309
6.11
References
310
7
Ser/Thr-specific Protein Kinases and Protein Phosphatases
313
7.1
Classification, Structure and Characteristics of
Protein Kinases
313
7.1.1
General Classification and Function of Protein Kinases
313
7.1.2
Classification of Ser/Thr-specific Protein Kinases
315
7.2
Structure and Regulation of Protein Kinases
316
7.2.1
Main Structural Elements of Protein Kinases
318
7.2.2
Substrate Binding and Recognition
321
7.2.3
Control of Protein Kinase Activity
322
7.2.4
Regulation of Protein Phosphorylation by Subcellular
Localization and Specific Targeting Subunits
325
73
PKA
327
7.3.1
Structure and Substrate Specificity of PKA
327
7.3.2
Regulation of PKA
329
7.3.3
AKAPs
330
7.4
Phosphatidylinositol-3-kinase (PI3K)/Akt Pathway
332
7.4.1
PI3K
332
7.4.2
PKB/Akt Kinase
335
7.5
PKC
338
7.5.1
Classification and Structure
338
7.,5.2
Activation of PKC by Cofactors
341
7.5.3
Regulation of PKC
341
7.5.4
Receptors for PKC and RACK (Receptors for Activated PKC)
Proteins
344
7.5.5
Functions and Substrates of PKC
345
7.6
Ca^/Calmodulin-dependent Protein Kinases (CaMKs)
346
7.6.1
Importance and General Function
346
7.6.2
CaMK II
347
7.7
Ser/Thr-specific Protein Phosphatases
351
7.7.1
Structure and Classification of Ser/Thr Protein
Phosphatases
351
7.7.2
Regulation of Ser/Thr Protein Phosphatases
352
7.7.3
PP1
353
7.7.4
PP2A
354
7.7.5
PP2B (Calcineurin)
356
7.8
References
359
XVI Contents
8
Signal Transmission via
Transmembrane
Receptors
with Tyrosine-Specific Protein Kinase Activity
361
8.1
Structure and Function of RTKs
363
8.1.1
General Structure and Classification
363
8.1.2
Ligand Binding and Receptor Dimerization
365
8.1.3
Structure and Activation of the Tyrosine
Kinase Domain
369
8.1.4
Effector Proteins of the RTKs
373
8.1.5
Attenuation and Termination of RTK Signaling
376
8.2
Protein Modules in Downstream Signaling of RTKs
379
8.2.1
Domains with Binding Specificity for Phosphotyrosine:
SH2,
PTB
and C2 Domains
381
8.2.2
SH3 Domains
384
8.2.3
Membrane-targeting Domains: Pleckstrin Homology (PH)
Domains and FYVE Domains
385
8.2.4
Phosphoserine/Threonine-binding Domains
386
8.2.5
PDZ Domains 3S7
8.3
Non-RTK-specific Protein Kinases
388
8.3.1
Structure and General Function of Non-RTKs
389
8.3.2
Src Tyrosine Kinase
390
8.3.3
АЫ
Tyrosine Kinase
392
8.4
PTPs
395
8.4.1
Structure and Classification of PTPs
396
8.4.2
Cooperation of PTPs and Protein Tyrosine Kinases
399
8.4.3
Regulation of PTPs
402
8.5
Adaptor Molecules of RTKs
404
8.6
References
408
9
Signal Transmission via
Ras
Proteins
411
9.1
Ras
Superfamily of
Monomeric
GTPases
411
9.2
GAPs of the
Monomeric
GTPases
413
9.3
GEFs of the
Monomeric
GTPases
414
9.4
Inhibitors of G-nucleotide dissociation GDIs
416
9.5
Ras
Family of
Monomeric
GTPases
427
9.5.1
General Properties of the
Ras
Protein
418
9.5.2
Structure of the GTP- and GDP-bound Forms of
Ras
Protein
429
9.5.3
GTP Hydrolysis Mechanism and Stimulation by
GAP Proteins
420
9.5.4
Structure and Biochemical Properties of
Transforming Mutants of
Ras
Protein
422
9.5.5
Membrane Localization of
Ras
Protein
423
9.5.6
GAPs in
Ras
Signal Transduction
424
9.5.7
GEFs in
Ras
Signal Transduction
424
Contents
XVII
9.6
Raf
Kinase as an Effector of Signal Transduction by
Ras
Proteins
427
9.6.1
Structure of
Raf
Kinase
427
9.6.2
Mechanism of Activation and Regulation of
Raf
Kinase
428
9.6.3
Oncogenic Activation of
Raf
430
9.7
Further
Ras
Family Members: R-Ras,
Ral
and Rap
430
9.8
Reception and Transmission of Multiple Signals by
Ras
Protein
431
9.8.1
Multiple Input Signals of
Ras
Protein
431
9.8.2
Multiple Effector Molecules of
Ras
Proteins
432
9.9
Further Branches of the
Ras Superfamily
434
9.9.1
Rho/Rac Family
434
9.9.2
Rab
Family
435
9.9.3
Ran Family
435
9.9.4
Arf Family
436
9.10
Ras
Protein Network and Crosstalk within the
Ras
Superfamily
436
9.11
References
439
Ί0
Intracellular Signal Transduction: Protein Cascades of
the Mitogen-activated Protein Kinase Pathways
441
10.1
Organization and Components of
МАРК
Pathways
443
10.2
Regulation of
МАРК
Pathways by Protein Phosphatases
and Inhibitory Proteins
446
10.3
Specificity in
МАРК
Activation and Organization in
Multiprotein Complexes
447
10.4
Major
МАРК
Pathways of Mammals
450
10.4.1
ERK Pathway
450
10.4.2
JNK and p38
МАРК
Pathways
451
10.5
References
456
11
Membrane Receptors with Associated Tyrosine
Kinase Activity
457
11.1
Cytokines and Cytokine Receptors
457
11.2
Structure and Activation of Cytokine Receptors
458
11.2.1
Activation of Cytoplasmic Tyrosine Kinases
465
11.2.2
The JAK-STAT Pathway
468
11.2.2.1
JAKs
468
11.2.2.2
STAT
Proteins
469
11.2.3
Regulation of Cytokine Receptor Signaling
472
11.3
Τ
and
В
Cell Receptors (TCRs and BCRs)
474
11.3.1
Receptor Structure
474
11.3.2
Intracellular Signal Molecules of the TCRs and BCRs
476
11.4
Signal Transduction via Integrins
478
11.5
References
482
XVIII
Contents
12
Other
Transmembrane
Receptor Classes
483
12.1
Receptors with Intrinsic Ser/Thr Kinase Activity:
TGF-ß
Receptor and SMAD Protein Signaling
484
12.1.1
Family of
TGF-ß
Cytokines
484
12.1.2 TGF-ß
Receptor
485
12.1.3
SMAD Proteins
486
12.2
Receptor Regulation by Intramembrane Proteolysis:
Notch Receptor
491
12.3
References
494
13
Regulation of the Cell Cycle
495
13.1
Principles of Cell Cycle Control
496
13.2
Key Elements of the Cell Cycle Apparatus
499
13.2.1
CDKs
499
13.2.2
Cyclins
502
13.2.3
CKIs
505
13.3
CDK-Cyclin Complexes
507
13.3.1
Structure of CDKs and CDK-Cydin complexes
508
13.3.2
Regulation of CDKs by Phosphorylation
509
13.3.3
Inhibition by CKIs
511
13.3.4
Substrates of CDKs
512
13.3.5
Multiple Regulation of CDKs
514
13.4
Regulation of the Cell Cycle by Proteolysis
515
13.4.1
Proteolysis mediated by the SCF Complex
536
13.4.2
Proteolysis mediated by the APC
517
13.5
Gj Progression and S-phase Entry
528
13.5.1
CDK4/6 and the D-type Cyclins
519
13.5.2
Central Function of CDO-Cyclin
E in
S-phase Entry
521
13.5.3
Function of Rb in the Cell Cycle
522
13.5.4
E2F Transcription Factors and their Control by Rb
523
13.5.5
Negative Regulation of the Gj/S Transition
526
13.6
Cell Cycle Control of
DNA
Replication
527
13.7
The G2/M Transition and CDC25C Phosphatase
529
13.8
Progression through the
M
phase:
APC and the Metaphase-Anaphase Transition
531
13.9
Summary of Cell Cycle Progression
533
13.10 DNA
Damage and
DNA
Replication Checkpoints
536
13.10.1
Components and Organization of
DNA
Damage Checkpoints
537
13.10.2
Mammalian Gj
DNA
Damage Checkpoint
539
13.10.3
S-phase Checkpoint Pathways
540
13.10.4
G2/M Checkpoint
540
13.11
References
541
Contents
XIX
14
Malfunction of Signaling Pathways and Tumorigenesis:
Oncogenes and Tumor Suppressor Genes
543
14.1
General Aspects of Tumor Formation
543
14.1.1
Characteristics of Tumor Cells
543
14.1.2
Genetic Changes in Tumor Cells
545
14.1.3
Epigenetic Changes in Tumor Cells
546
14.2
Signaling Proteins Mutated in Cancer: Oncogenes
548
14.2.1
Mechanisms of
Oncogene
Activation
549
14.2.2
Examples of the Functions of Oncogenes
552
14.3
Tumor Suppressor Genes: General Functions
558
14.4
Rb in Cancer
559
14.5
pl6INK4a Gene Locus and ARF
564
14.6
Tumor Suppressor Protein p53
565
14.6.1
Structure and Biochemical Properties of p53
565
14.6.2
Structure of p53 and its
DNA
Complex
567
14.6.3
Posrtranslational Modification of p53
567
14.6.4
Genes Regulated by p53
570
14.6.5
Regulation of p53 by Ubiquitination and Proteasomal
Degradation: The MDM2 Protein
573
14.6.6
Pathways Involved in Activation of p53
575
14.6.7
The
MDM2-p53
Network and Cancer
578
14.7 Wnt/ß-Catenin
Signaling and the Tumor Suppressor
APC
578
14.8
Genomic instability and Tumor Formation: Roles of
DNA
Repair and
DNA
Damage Checkpoints
580
14.9
Common Physiologic Changes in Tumor Cells: Hallmarks of
Cancer
582
14.9.1
Self-sufficiency in Growth Signals
583
14.9.2
Insensitiviry to Antigrowth Signals
584
14.9.3
Evasion of Programmed Cell Death (Apoptosis)
585
14.9.4
Limitless
Replicative
Potential of Cancer Cells
586
14.10
References
587
15
Apoptosis
589
15.1
Basic Functions of Apoptosis
589
15.2
Overview of Apoptotic Pathways
59Í
15.3
Caspases: Death by Proteolysis
592
15.3.1
Initiator and Effector Caspases
593
15.3.2
Mechanism of Caspases
594
15.3.3
Caspase Activation and Regulation
596
15.4
Bcl-2 Proteins Family: Gatekeepers of Apoptosis
599
15.5
The Mitochondrial Pathway of Apoptosis
602
XX
Contents
15.6
Death Receptor-triggered Apoptosis
606
15.6.1
Fas/CDOS Signaling Pathway
607
15.6.2
TNFR1 and Apoptosis
609
15.7
Links of Apoptosis to Cellular Signaling Pathways
620
15.7.1
Phosphatidylinositol-3-kinase (PI3K)/Akt Kinase
and Apoptosis
611
15.7.2
p53 and Apoptosis
622
15.8
References
615
Subject Index
627
|
| adam_txt |
IX
Contents
Preface VII
1
Basics of Cell Signaling
1
1.1
Cell Signaling: Why, When and Where?
1
1.2
Intercellular Signaling
3
1.2.1
Tools for Intercellular Signaling
3
1.2.2
Steps of Intercellular Signaling
S
1.2.3
Regulation of Intercellular Signaling
7
1.3
Hormones in Intercellular Signaling
8
1.3.1
Chemical Nature of Hormones
8
1.3.2
Hormone Analogs: Agonists and Antagonists
12
1.3.3
Endocrine, Paracrine and
Autocrine
Signaling
13
1.3.4
Direct Protein Modification by Signaling Molecules
25
1.4
Intracellular Signaling: Basics
í
5
1.4.1
Reception of External Signals IS
1.4.2
Activation and Deactivation of Signaling Proteins ?6
1.4.3
Processing of Multiple Signals
17
1.4.4
Variability of Signaling Proteins
17
1.5
Molecular Tools for Intracellular Signaling
18
1.5.1
Receptors
18
1.5.2
Signaling Enzymes
21
1.5.3
Adaptors and Scaffolding Proteins
22
1.5.4
Diffusible Intracellular Messengers: Second Messengers
22
1.6
Basic Mechanisms of Intracellular Signaling
24
1.6.1
Regulatory Modifications
24
1.6.2
Recognition of Protein Modifications by
Modification-specific Protein Modules
25
1.6.3
Multisite Protein Modification
26
1.6.4
Protein Interaction Domains
28
1.7
Modular Structure of Signaling Proteins and
Signaling Complexes
32
1.7.1
Modules in Signaling Proteins
32
1.7.2
Modular Signaling Complexes
33
Χ ι
Contents
1.8
Organization of Signaling
34
1.8.1
Linear Signaling Pathways, Branching and Crosstalk
35
1.8.1.1
Linear Pathways
35
1.8.1.2
Branching and Crosstalk
37
1.8.1.3
Interactions between Signaling Paths
37
1.8.2
Signaling Networks
38
1.8.2.1
Complexity of Signaling Networks
39
1.8.2.2
Properties of Signaling Networks
39
1.8.2.3
Nodes and Junctions
41
1.8.2.4
Feedback Loops
42
1.8.3
Redundancy and Specificity of Signaling
46
1.8.4
Regulation of Signaling Pathways
47
1.8.5
Spatial Organization of Signaling Pathways
49
1.8.6
Compartmentalization and Transport
50
1.8.7
Evolution of Signaling Pathways
51
1.9
Variability and Cell-type Specificity of Signaling
51
1.10
References
53
2
Regulation of Enzyme Activity
55
2.1
Basis of Enzyme Catalysis
56
2.2
Basics of Allosteric Regulation
58
2.3
Regulation of Enzymes by Effector Molecules
60
2.4
Regulation of Enzyme Activity by Phosphorylation
62
2.5
"Ubiquitin
(Ub)-Proteasome"
Pathway
64
2.5.1
Components of the Ub System
65
2.5.2
Ub and Ub-like Proteins
66
2.5.3
Activation and Transacylation of Ub:
El and E2 Enzymes
67
2.5.4
Transfer to the Target Protein with the Participation
of E3
69
2.5.5
HECT Domain E3 Enzymes
71
2.5.6
RING Domain E3 Enzymes
72
2.5.6.1
N-end Rule Enzymes
73
2.5.6.2
Cbl Protein
73
2.5.6.3
Cullin-based E3 Enzymes, SCF and APC
74
2.5.6.4
Processing of Nuclear Factor
(NF) kB
and Degradation
of IkB
76
2.5.7
Degradation in the Proteasome
78
2.5.8
Other Regulatory Functions of Ub Conjugation
80
2.5.9
Regulation of Proteins by Sumoylation
82
2.6
Lipidation of Signaling Proteins
83
2.6.1
Myristoylation
84
2.6.2
Palmitoylarion
85
2.6.3
Farnesylation and Geranylation
86
2.6.4
Dual Lipidation
87
Contents
XI
2.6.5
Cholesterol
Membrane
Anchor
88
2.6.6 Switch
Function of
Lipid
Anchors
88
2.6.7
Glycosylphosphatidylinositol (GPI) Anchor
90
2.7
References
91
3
Regulation of Gene Expression
93
3.1
Basic Steps of Gene Expression
93
3.2
Components of the Eukaryotic Transcription Machinery
95
3.2.1
Basic Features of Eukaryotic Transcription
96
3.2.2
Elementary Steps of Eukaryotic Transcription
98
3.2.3
Eukaryotic
RNA Polymerases
98
3.2.4
Structure of the Transcription Start Site and
Regulatory Sequences
100
3.2.5
General Transcription Factors and the
Core Transcription Apparatus
101
3.2.6
Holoenzyme Forms of
RNA
Pol II
103
3.2.7
Phosphorylation of
RNA Pol
II and the Onset
of Transcription
204
3.2.8
TFIIH
-
A Pivotal Regulatory Protein Complex
106
3.2.9
Mediator Complex
107
3.3
Principles of Transcription Regulation
109
3.3.1
Elements of Transcription Regulation
109
3.3.2
Regulation of Eukaryotic Transcription by Sequence-specific
DNA-binding Proteins 111
3.3.3 DNA
Binding of Transcriptional Regulators
112
3.3.4
Structure of the Recognition Sequence and Quaternary
Structure of DNA-binding Proteins
113
3.3.5
Communication with the Transcription Apparatus:
Transactivation Domains
115
3.3.6
Families of Sequence-specific Transcription Factors and
Homo- or Heterodimerization
126
3.4
Control of Transcription Factors
118
3.4.1
Mechanisms for the Control of Regulatory DNA-binding
Proteins
278
3.4.2
Changes in the Concentration of Regulatory DNA-binding
Proteins
119
3.4.3
Regulation by Binding of Effector Molecules
329
3.4.4
Posttranslational Modification of Transcription
Regulators
220
3.4.5
Regulation by Phosphorylation
221
3.4.6
Regulation by Methylation, Acetylation and
Redox
Modification
225
XII Contents
3.4.7 Transcriptional Regulation in
the
Framework
of
Signal Transduction Networks 125
3.4.7.1 Constitutively Active
Transcription Factors
126
3.4.7.2
Regulatory Transcription Factors
126
3.4.8
Repression of Transcription
128
3.4.9
Coregulators of Transcription
130
3.5
Chromatin Structure and Transcription Regulation
131
3.5.1
Nucleosome and Chromatin Structure
132
3.5.2
Histone Acetylation and Deacetylation
134
3.5.3
Histone Methylation
136
3.5.3.1
Histone
Arginine
Methylation
136
3.5.3.2
Arginine Demethylation/Citrullination
138
3.5.3.3
Histone
Lysine
Methylation
138
3.5.3.4
Histone
Lysine
Demethylation
139
3.5.4
Histone Phosphorylation
140
3.5.5
Histone Ubiquitination and Sumoylation
141
3.5.6
Histone Modification "Code"
141
3.5.7
Recognition of Histone Modifications by
Protein Domains
143
3.5.8 DNA
Methylation
144
3.5.9
Summary of the Regulatory Steps in Transcription
148
3.6
Posttranscriptional Regulation of Gene Expression
150
3.6.1
Control at the Level of Pre-mRNA Processing
351
3.6.2
Stability of mRNA
155
3.6.3
Regulation at the Level of Translation
157
3.6.3.1
General Mechanisms of Translational Control
157
3.6.3.2
mRNA-specific Regulation by
5'
Sequences:
Control of Ferritin mRNA Translation by Iron
159
3.6.3.3
mRNA-specific Translational Regulation by
Protein Binding to
3'
-Untranslated Regions
160
3.6.3.4
Global Translational Regulation of mRNAs by
Targeting
ЄІР-4Е
162
3.6.3.5
Regulation of Translation via elF-2
164
3.7
Regulation by
RNA
Interference (RNAi)
167
3.7.1
Small Regulatory RNAs
170
3.7.2
Incorporation of Small RNAs into RISC
172
3.7.3
Cleaving the Target
RNA
173
3.7.4
Specificity and Target Selection in RNAi
175
3.7.5
Biological Functions of RNAi
176
3.7.5.1
Functions and Applications of siRNAs
176
3.7.5.2
Functions of miRNAs
176
3.7.5.3
RISCs and Chromatin Structure
177
3.8
References
179
Contents
XIII
4
Signaling by Nuclear Receptors
181
4.1
Ligands of Nuclear Receptors
181
4.2
Principles of Signaling by Nuclear Receptors
184
4.3
Classification and Structure of Nuclear Receptors
186
4.3.1
DNA-binding Elements of Nuclear Receptors: HREs
187
4.3.2
The DNA-binding Domain of Nuclear Receptors
189
4.3.3
HRE
Recognition and Structure of the HRE-Receptor
Complex
190
4.3.4
Ligand-binding Domain (LBD)
191
4.3.5
Transactivating Elements of the Nuclear Receptors
195
4.4
Mechanisms of Transcriptional Regulation by
Nuclear Receptors
196
4.4.1
Steroid Receptor Coactivator (SRC)-l/pl60 and
Thyroid Hormone Receptor-activating Protein (TRAP)
Coactivators
198
4.4.2
Corepressors of Nuclear Receptors
200
4.5
Regulation of Signaling by Nuclear Receptors
200
4.6
The Signaling Pathway of the Steroid Hormone
Receptors
203
4.7
Signaling by Retinoids, Vitamin D3 and the
T3 Hormone
205
4.8
Nongenomic Functions of Nuclear Receptors and
their Ligands
207
4.9
References
211
5
G-protein-coupled Signal Transmission Pathways
213
5.1 Transmembrane (TM)
Receptors: General Structure and
Classification
213
5.2
Structural Principles of TM Receptors
215
5.2.1
The Extracellular Domain of TM Receptors
217
5.2.2
TM Domain
217
5.2.3
Intracellular Domain of Membrane Receptors
219
5.2.4
Regulation of Receptor Activity
221
5.3
GPCRs
222
5.3.1
Classification of GPCRs
223
5.3.2
Structure of GPCRs
225
5.3.3
Ligand Binding and Mechanism of
Signal Transmission
227
5.3.4
Regulation of GPCRs
228
5.3.5
Switching Off and Desensitization of 7TM Receptors
229
5.3.6
Dimerization of GPCRs
233
5.4
Regulatory GTPases
233
5.4.1
The GTPase Superfamily: General Functions and
Mechanism
234
5.4.2
Inhibition of GTPases by GTP Analogs
236
XIV Contents
5.4.3
The G-domain as a Common Structural Element of
the GTPases
237
5.4.4
GTPase Families
238
5.5
Heterotrimeric G-proteins
239
5.5.1
Classification of the Heterotrimeric G-proteins
240
5.5.2
Toxins as Tools in the Characterization of
Heterotrimeric G-proteins
243
5.5.3
Functional Cycle of Heterotrimeric G-proteins
244
5.5.4
Structural and Mechanistic Aspects of the Switch Function
of G-proteins
247
5.5.5
Structure and Function of the
βγ
-Complex
253
5.5.6
Membrane Association of the G-proteins
255
5.5.7
Regulators of G-proteins: Phosducin and RG
S
Proteins
256
5.6
Receptor-independent Functions of Heterotrimeric
G-proteins
259
5.7
Effector Molecules of G-proteins
259
5.7.1
Adenylyl Cyclase and cAMP as "Second Messenger"
260
5.7.2
PLC
264
5.8
GPCR Signaling via
Arrestin 26S
5.9
References
269
6
Intracellular Messenger Substances: "Second Messengers"
271
6.1
General Properties of Intracellular Messenger
Substances
272
6.2
cAMP
273
6.3
cGMP and Guanylyl Cyclases
275
6.3.1
Guanylyl Cyclases
276
6.3.2
Targets of cGMP
277
6.4
Metabolism of Inositol Phospholipids and
Inositol Phosphates
278
6.5
Storage and Release of Ca2+
282
6.5.1
Release of Ca2+ from Ca2+ Storage
282
6.5.2
Influx of Ca2+ from the Extracellular Region
288
6.5.3
Removal and Storage of Ca2+
288
6.5.4
Temporal and Spatial Changes in Ca2+ Concentration
289
6.6
Functions of Phosphoinositides
290
6.6.1
Messenger Function of PtdIns(3,4,5)P3
291
6.6.2
Functions of PtdIns(4,5)P2 and other
Phosphoinositides
291
6.7
Ca2+ as a Signal Molecule
292
6.7.1
Calmodulin as a Ca2+ Sensor
295
6.7.2
Target Proteins of Ca^/Calmodulin
297
6.7.3
Other Ca2+ Sensors
298
6.8
DAG as a Signal Molecule
299
6.9
Other
Lipid
Messengers
300
Contents
I XV
6.10
NO Signaling Molecule
301
6.10.1
Reactivity of NO
302
6.10.2
Synthesis of NO
303
6.10.3
Physiological Functions of Nitrosylation
305
6.10.3.1
Nitrosylation of Metal Centers
305
6.10.3.2
Regulatory Functions of
S
-Nitrosylation
307
6.10.3.3
Toxic Action of NO and Nitrosative Stress
309
6.11
References
310
7
Ser/Thr-specific Protein Kinases and Protein Phosphatases
313
7.1
Classification, Structure and Characteristics of
Protein Kinases
313
7.1.1
General Classification and Function of Protein Kinases
313
7.1.2
Classification of Ser/Thr-specific Protein Kinases
315
7.2
Structure and Regulation of Protein Kinases
316
7.2.1
Main Structural Elements of Protein Kinases
318
7.2.2
Substrate Binding and Recognition
321
7.2.3
Control of Protein Kinase Activity
322
7.2.4
Regulation of Protein Phosphorylation by Subcellular
Localization and Specific Targeting Subunits
325
73
PKA
327
7.3.1
Structure and Substrate Specificity of PKA
327
7.3.2
Regulation of PKA
329
7.3.3
AKAPs
330
7.4
Phosphatidylinositol-3-kinase (PI3K)/Akt Pathway
332
7.4.1
PI3K
332
7.4.2
PKB/Akt Kinase
335
7.5
PKC
338
7.5.1
Classification and Structure
338
7.,5.2
Activation of PKC by Cofactors
341
7.5.3
Regulation of PKC
341
7.5.4
Receptors for PKC and RACK (Receptors for Activated PKC)
Proteins
344
7.5.5
Functions and Substrates of PKC
345
7.6
Ca^/Calmodulin-dependent Protein Kinases (CaMKs)
346
7.6.1
Importance and General Function
346
7.6.2
CaMK II
347
7.7
Ser/Thr-specific Protein Phosphatases
351
7.7.1
Structure and Classification of Ser/Thr Protein
Phosphatases
351
7.7.2
Regulation of Ser/Thr Protein Phosphatases
352
7.7.3
PP1
353
7.7.4
PP2A
354
7.7.5
PP2B (Calcineurin)
356
7.8
References
359
XVI Contents
8
Signal Transmission via
Transmembrane
Receptors
with Tyrosine-Specific Protein Kinase Activity
361
8.1
Structure and Function of RTKs
363
8.1.1
General Structure and Classification
363
8.1.2
Ligand Binding and Receptor Dimerization
365
8.1.3
Structure and Activation of the Tyrosine
Kinase Domain
369
8.1.4
Effector Proteins of the RTKs
373
8.1.5
Attenuation and Termination of RTK Signaling
376
8.2
Protein Modules in Downstream Signaling of RTKs
379
8.2.1
Domains with Binding Specificity for Phosphotyrosine:
SH2,
PTB
and C2 Domains
381
8.2.2
SH3 Domains
384
8.2.3
Membrane-targeting Domains: Pleckstrin Homology (PH)
Domains and FYVE Domains
385
8.2.4
Phosphoserine/Threonine-binding Domains
386
8.2.5
PDZ Domains 3S7
8.3
Non-RTK-specific Protein Kinases
388
8.3.1
Structure and General Function of Non-RTKs
389
8.3.2
Src Tyrosine Kinase
390
8.3.3
АЫ
Tyrosine Kinase
392
8.4
PTPs
395
8.4.1
Structure and Classification of PTPs
396
8.4.2
Cooperation of PTPs and Protein Tyrosine Kinases
399
8.4.3
Regulation of PTPs
402
8.5
Adaptor Molecules of RTKs
404
8.6
References
408
9
Signal Transmission via
Ras
Proteins
411
9.1
Ras
Superfamily of
Monomeric
GTPases
411
9.2
GAPs of the
Monomeric
GTPases
413
9.3
GEFs of the
Monomeric
GTPases
414
9.4
Inhibitors of G-nucleotide dissociation GDIs
416
9.5
Ras
Family of
Monomeric
GTPases
427
9.5.1
General Properties of the
Ras
Protein
418
9.5.2
Structure of the GTP- and GDP-bound Forms of
Ras
Protein
429
9.5.3
GTP Hydrolysis Mechanism and Stimulation by
GAP Proteins
420
9.5.4
Structure and Biochemical Properties of
Transforming Mutants of
Ras
Protein
422
9.5.5
Membrane Localization of
Ras
Protein
423
9.5.6
GAPs in
Ras
Signal Transduction
424
9.5.7
GEFs in
Ras
Signal Transduction
424
Contents
XVII
9.6
Raf
Kinase as an Effector of Signal Transduction by
Ras
Proteins
427
9.6.1
Structure of
Raf
Kinase
427
9.6.2
Mechanism of Activation and Regulation of
Raf
Kinase
428
9.6.3
Oncogenic Activation of
Raf
430
9.7
Further
Ras
Family Members: R-Ras,
Ral
and Rap
430
9.8
Reception and Transmission of Multiple Signals by
Ras
Protein
431
9.8.1
Multiple Input Signals of
Ras
Protein
431
9.8.2
Multiple Effector Molecules of
Ras
Proteins
432
9.9
Further Branches of the
Ras Superfamily
434
9.9.1
Rho/Rac Family
434
9.9.2
Rab
Family
435
9.9.3
Ran Family
435
9.9.4
Arf Family
436
9.10
Ras
Protein Network and Crosstalk within the
Ras
Superfamily
436
9.11
References
439
Ί0
Intracellular Signal Transduction: Protein Cascades of
the Mitogen-activated Protein Kinase Pathways
441
10.1
Organization and Components of
МАРК
Pathways
443
10.2
Regulation of
МАРК
Pathways by Protein Phosphatases
and Inhibitory Proteins
446
10.3
Specificity in
МАРК
Activation and Organization in
Multiprotein Complexes
447
10.4
Major
МАРК
Pathways of Mammals
450
10.4.1
ERK Pathway
450
10.4.2
JNK and p38
МАРК
Pathways
451
10.5
References
456
11
Membrane Receptors with Associated Tyrosine
Kinase Activity
457
11.1
Cytokines and Cytokine Receptors
457
11.2
Structure and Activation of Cytokine Receptors
458
11.2.1
Activation of Cytoplasmic Tyrosine Kinases
465
11.2.2
The JAK-STAT Pathway
468
11.2.2.1
JAKs
468
11.2.2.2
STAT
Proteins
469
11.2.3
Regulation of Cytokine Receptor Signaling
472
11.3
Τ
and
В
Cell Receptors (TCRs and BCRs)
474
11.3.1
Receptor Structure
474
11.3.2
Intracellular Signal Molecules of the TCRs and BCRs
476
11.4
Signal Transduction via Integrins
478
11.5
References
482
XVIII
Contents
12
Other
Transmembrane
Receptor Classes
483
12.1
Receptors with Intrinsic Ser/Thr Kinase Activity:
TGF-ß
Receptor and SMAD Protein Signaling
484
12.1.1
Family of
TGF-ß
Cytokines
484
12.1.2 TGF-ß
Receptor
485
12.1.3
SMAD Proteins
486
12.2
Receptor Regulation by Intramembrane Proteolysis:
Notch Receptor
491
12.3
References
494
13
Regulation of the Cell Cycle
495
13.1
Principles of Cell Cycle Control
496
13.2
Key Elements of the Cell Cycle Apparatus
499
13.2.1
CDKs
499
13.2.2
Cyclins
502
13.2.3
CKIs
505
13.3
CDK-Cyclin Complexes
507
13.3.1
Structure of CDKs and CDK-Cydin complexes
508
13.3.2
Regulation of CDKs by Phosphorylation
509
13.3.3
Inhibition by CKIs
511
13.3.4
Substrates of CDKs
512
13.3.5
Multiple Regulation of CDKs
514
13.4
Regulation of the Cell Cycle by Proteolysis
515
13.4.1
Proteolysis mediated by the SCF Complex
536
13.4.2
Proteolysis mediated by the APC
517
13.5
Gj Progression and S-phase Entry
528
13.5.1
CDK4/6 and the D-type Cyclins
519
13.5.2
Central Function of CDO-Cyclin
E in
S-phase Entry
521
13.5.3
Function of Rb in the Cell Cycle
522
13.5.4
E2F Transcription Factors and their Control by Rb
523
13.5.5
Negative Regulation of the Gj/S Transition
526
13.6
Cell Cycle Control of
DNA
Replication
527
13.7
The G2/M Transition and CDC25C Phosphatase
529
13.8
Progression through the
M
phase:
APC and the Metaphase-Anaphase Transition
531
13.9
Summary of Cell Cycle Progression
533
13.10 DNA
Damage and
DNA
Replication Checkpoints
536
13.10.1
Components and Organization of
DNA
Damage Checkpoints
537
13.10.2
Mammalian Gj
DNA
Damage Checkpoint
539
13.10.3
S-phase Checkpoint Pathways
540
13.10.4
G2/M Checkpoint
540
13.11
References
541
Contents
XIX
14
Malfunction of Signaling Pathways and Tumorigenesis:
Oncogenes and Tumor Suppressor Genes
543
14.1
General Aspects of Tumor Formation
543
14.1.1
Characteristics of Tumor Cells
543
14.1.2
Genetic Changes in Tumor Cells
545
14.1.3
Epigenetic Changes in Tumor Cells
546
14.2
Signaling Proteins Mutated in Cancer: Oncogenes
548
14.2.1
Mechanisms of
Oncogene
Activation
549
14.2.2
Examples of the Functions of Oncogenes
552
14.3
Tumor Suppressor Genes: General Functions
558
14.4
Rb in Cancer
559
14.5
pl6INK4a Gene Locus and ARF
564
14.6
Tumor Suppressor Protein p53
565
14.6.1
Structure and Biochemical Properties of p53
565
14.6.2
Structure of p53 and its
DNA
Complex
567
14.6.3
Posrtranslational Modification of p53
567
14.6.4
Genes Regulated by p53
570
14.6.5
Regulation of p53 by Ubiquitination and Proteasomal
Degradation: The MDM2 Protein
573
14.6.6
Pathways Involved in Activation of p53
575
14.6.7
The
MDM2-p53
Network and Cancer
578
14.7 Wnt/ß-Catenin
Signaling and the Tumor Suppressor
APC
578
14.8
Genomic instability and Tumor Formation: Roles of
DNA
Repair and
DNA
Damage Checkpoints
580
14.9
Common Physiologic Changes in Tumor Cells: Hallmarks of
Cancer
582
14.9.1
Self-sufficiency in Growth Signals
583
14.9.2
Insensitiviry to Antigrowth Signals
584
14.9.3
Evasion of Programmed Cell Death (Apoptosis)
585
14.9.4
Limitless
Replicative
Potential of Cancer Cells
586
14.10
References
587
15
Apoptosis
589
15.1
Basic Functions of Apoptosis
589
15.2
Overview of Apoptotic Pathways
59Í
15.3
Caspases: Death by Proteolysis
592
15.3.1
Initiator and Effector Caspases
593
15.3.2
Mechanism of Caspases
594
15.3.3
Caspase Activation and Regulation
596
15.4
Bcl-2 Proteins Family: Gatekeepers of Apoptosis
599
15.5
The Mitochondrial Pathway of Apoptosis
602
XX
Contents
15.6
Death Receptor-triggered Apoptosis
606
15.6.1
Fas/CDOS Signaling Pathway
607
15.6.2
TNFR1 and Apoptosis
609
15.7
Links of Apoptosis to Cellular Signaling Pathways
620
15.7.1
Phosphatidylinositol-3-kinase (PI3K)/Akt Kinase
and Apoptosis
611
15.7.2
p53 and Apoptosis
622
15.8
References
615
Subject Index
627 |
| any_adam_object | 1 |
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| author | Krauss, Gerhard 1943- |
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| classification_tum | BIO 200f BIO 220f CHE 800f |
| ctrlnum | (OCoLC)229444435 (DE-599)BVBBV022783684 |
| dewey-full | 571.74 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.74 |
| dewey-search | 571.74 |
| dewey-sort | 3571.74 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Chemie |
| discipline_str_mv | Biologie Chemie |
| edition | 4. enlarged and improved ed. |
| format | Book |
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| genre | (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Lehrbuch |
| id | DE-604.BV022783684 |
| illustrated | Illustrated |
| index_date | 2024-07-02T18:37:12Z |
| indexdate | 2024-07-09T21:06:04Z |
| institution | BVB |
| isbn | 9783527313976 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-015989147 |
| oclc_num | 229444435 |
| open_access_boolean | |
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| physical | XX, 626 S. Ill., graph. Darst. |
| publishDate | 2008 |
| publishDateSearch | 2008 |
| publishDateSort | 2008 |
| publisher | Wiley-VCH |
| record_format | marc |
| spelling | Krauss, Gerhard 1943- Verfasser (DE-588)133839915 aut Biochemistry of signal transduction and regulation Gerhard Krauss 4. enlarged and improved ed. Weinheim Wiley-VCH 2008 XX, 626 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Regulation (DE-588)4049075-0 gnd rswk-swf Molekularbiologie (DE-588)4039983-7 gnd rswk-swf Signaltransduktion (DE-588)4318717-1 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Signaltransduktion (DE-588)4318717-1 s Regulation (DE-588)4049075-0 s Molekularbiologie (DE-588)4039983-7 s 1\p DE-604 b DE-604 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015989147&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Krauss, Gerhard 1943- Biochemistry of signal transduction and regulation Regulation (DE-588)4049075-0 gnd Molekularbiologie (DE-588)4039983-7 gnd Signaltransduktion (DE-588)4318717-1 gnd |
| subject_GND | (DE-588)4049075-0 (DE-588)4039983-7 (DE-588)4318717-1 (DE-588)4123623-3 |
| title | Biochemistry of signal transduction and regulation |
| title_auth | Biochemistry of signal transduction and regulation |
| title_exact_search | Biochemistry of signal transduction and regulation |
| title_exact_search_txtP | Biochemistry of signal transduction and regulation |
| title_full | Biochemistry of signal transduction and regulation Gerhard Krauss |
| title_fullStr | Biochemistry of signal transduction and regulation Gerhard Krauss |
| title_full_unstemmed | Biochemistry of signal transduction and regulation Gerhard Krauss |
| title_short | Biochemistry of signal transduction and regulation |
| title_sort | biochemistry of signal transduction and regulation |
| topic | Regulation (DE-588)4049075-0 gnd Molekularbiologie (DE-588)4039983-7 gnd Signaltransduktion (DE-588)4318717-1 gnd |
| topic_facet | Regulation Molekularbiologie Signaltransduktion Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015989147&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT kraussgerhard biochemistryofsignaltransductionandregulation |