Handbook of growth factors. Volume 1, General basic aspects

383 Pages·35.328 MB·English

by  Pimentel, Enrique

Handbook of
GROWTH FACTORS
Volume I: General Basic Aspects
HANDBOOK OF GROWTH FACTORS
Enrique Pimentel, M.D.
Volume I
General Basic Aspects
Regulation of Cell Functions
Growth Factor Receptors
Postreceptor Mechanisms of Growth Factor Action
Cyclic Nucleotides
Guanosine Triphosphate-Binding Proteins
The Calcium-Calmodulin System
Phosphoinositide Metabolism
Protein Phosphorylation
Proto-Oncogene and Onco-Suppressor Gene Expression
Role of Growth Factors in Neoplastic Processes
Volume II
Peptide Growth Factors
Insulin
Insulin-Like Growth Factors
Epidermal Growth Factor
Fibroblast Growth Factors
Neurotrophic Growth Factors
Organ-Specific Growth Factors
Cell-Specific Growth Factors
Transforming Growth Factors
Regulatory Peptides with Growth Factor-Like Properties
Volume III
Hematopoietic Growth Factors and Cytokines
Hematopoietic Growth Factors
Interleukins and Cytokines
Colony-Stimulating Factors
Interferons
Tumor Necrosis Factors
Erythropoietic Growth Factors
Platelet-Derived Growth Factor
Transferrins
Handbook of
GROWTH FACTORS
Volume I: General Basic Aspects
Enrique Pimentel, M.D.
National Center of Genetics
Institute of Experimental Medicine
Central University of Venezuela
Caracas, Venezuela
First published 1994 by CRC Press
Taylor & Francis Group
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Reissued 2018 by CRC Press
© 1994 by Taylor & Francis
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CONTENTS
Chapter 1
Regulation of Cell Functions
I. Introduction............................................................................................................................................1
II. The Cell Cycle........................................................................................................................................2
A. Phases of the Cell Cycle.................................................................................................................2
B. Regulation of the Cell Cycle...........................................................................................................3
C. Cellular Senescence.........................................................................................................................7
D. Apoptosis..........................................................................................................................................7
E. Cellular Immortalization.................................................................................................................8
III. Regulation of Cell Proliferation and Differentiation.........................................................................9
A. Role of Growth Factors in Developmental Processes...................................................................9
B. Regulation of Homeobox-Containing Genes..............................................................................10
C. Competence and Progression Factors..........................................................................................11
D. Cellular Responses to Growth Factors.........................................................................................12
E. Regulation of Differentiated Functions by Growth Factors........................................................13
F. Growth Factor-Like Proteins.........................................................................................................13
G. Proliferation-Associated Cellular Proteins...................................................................................14
H. Mechanisms of Regulation of Cell Proliferation by Growth Factors......................................15
1. Gene Expression During the Cell Cycle..................................................................................15
2. Cyclins.......................................................................................................................................18
3. The cdc2 and cdk2 Protein Kinases.......................................................................................20
4. Transcription Factors................................................................................................................23
5. Heat Shock Proteins.................................................................................................................24
I. Differentiation-Inducing Factors..................................................................................................26
1. Osteogenin.................................................................................................................................26
2. Preadipocyte-Stimulating Factor.............................................................................................26
3. Leukemia-Related Differentiation Inducers...........................................................................26
4. Leukemia Inhibitory Factor.....................................................................................................27
5. Other Differentiation Inducers................................................................................................27
6. Mechanisms of Cell Differentiation.......................................................................................28
J. Differentiation-Inhibiting Factors................................................................................................29
K. Growth-Inhibiting Factors.............................................................................................................29
1. GIFs Produced by Normal Cells.............................................................................................30
2. GIFs Produced by Neoplastic Cells.......................................................................................33
3. Physiological Role of GIFs.....................................................................................................34
4. Role of GIFs in Oncogenesis..................................................................................................34
IV. Growth Factors as Mediators of Hormone Action..........................................................................34
A. Growth Hormone...........................................................................................................................35
1. The Growth Hormone Receptor..............................................................................................35
2. Somatomedins...........................................................................................................................36
B. Thyroid Hormone..........................................................................................................................37
1. Thyroid Hormone Receptors...................................................................................................37
2. Growth Factors as Mediators of Thyroid Hormone Action..................................................39
C. Steroid Hormones..........................................................................................................................39
1. Steroid Hormone Receptors....................................................................................................39
2. Growth Factors as Mediators of Steroid Hormone Action...................................................40
References.......................................................................................................................................................42
Chapter 2
Growth Factor Receptors
I. Introduction...........................................................................................................................................73
II. Growth Factor Receptors....................................................................................................................73
A. Regulation of Receptor Expression..............................................................................................74
B. Receptor Phosphorylation............................................................................................................75
C. Mobility and Internalization of Surface Receptors....................................................................75
D. Receptor Expression in Neoplastic Cells...................................................................................76
References........................................................................................................................................................77
Chapter 3
Postreceptor Mechanisms of Growth Factor Action
I. Introduction...........................................................................................................................................81
II. Mediators and Modulators of Growth Factor Action......................................................................81
A. Prostaglandins.................................................................................................................................81
1. Physiological Role of Prostaglandins...................................................................................82
2. Cellular Mechanisms of Action of Prostaglandins..............................................................82
3. Role of Prostaglandins in Tumors.........................................................................................82
B. Leukotrienes ...................................................................................................................................83
C. Poly amines......................................................................................................................................84
1. Regulation of Ornithine Decarboxylase.................................................................................84
2. Mechanisms of Action of Polyamines...................................................................................85
3. Role of Poly amines in Oncogenesis......................................................................................86
III. Ion and pH Changes............................................................................................................................86
A. Ion Fluxes and Cytoplasmic pH...................................................................................................86
B. Mechanism of Na+/H+ Exchange Regulation..............................................................................87
C. Influence of Mitogens, Hormones, and Growth Factors...........................................................87
D. Regulation of Cell Cycle-Associated Events..............................................................................88
E. Influence of Oncogenes.................................................................................................................88
F. Expression of a Transformed Phenotype....................................................................................89
G. Role of Magnesium.......................................................................................................................89
References........................................................................................................................................................90
Chapter 4
Cyclic Nucleotides
I. Introduction...........................................................................................................................................97
II. Cyclic AMP and the Adenylyl Cyclase System..............................................................................97
A. The Adenylyl Cyclase System.....................................................................................................97
1. The Adenylyl Cyclase Family................................................................................................98
2. Regulation of the Adenylyl Cyclase System.........................................................................98
3. Role of cAMP in Hormone and Growth Factor Action.......................................................99
4. Role of cAMP in the Regulation of Gene Expression.........................................................99
B. cAMP-Dependent Protein Kinases.............................................................................................100
1. C Subunits of cAMP-Dependent Protein Kinases...............................................................101
2. R Subunits of cAMP-Dependent Protein Kinases..............................................................101
3. Regulatory Actions of cAMP-Dependent Protein Kinases.................................................102
4. Regulation of cAMP-Dependent Protein Kinase Activity.................................................102
C. The Adenylyl Cyclase System and Oncogenes........................................................................103
D. Role of the Adenylyl Cyclase System in Neoplasia..............................................................104
III. Cyclic GMP and the Guanylyl Cyclase System.............................................................................106
A. Guanylyl Cyclase..........................................................................................................................106
B. cGMP and Cell Proliferation.......................................................................................................106
C. cGMP-Dependent Protein Kinase..............................................................................................106
References......................................................................................................................................................107
Chapter 5
Guanosine Triphosphate-Binding Proteins
I. Introduction..........................................................................................................................................115
II. G Proteins..........................................................................................................................................115
A. G Protein Subunits......................................................................................................................116
B. Regulation of G Protein Expression..........................................................................................118
C. The G Protein-Coupled Receptor Family..................................................................................118
D. Alterations of G Proteins in Human Diseases..........................................................................119
III. The Ras Proteins.............................................................................................................................119
A. Regulation of ras Gene Expression...........................................................................................120
B. The Mammalian Ras Protein Superfamily................................................................................120
C. Structural and Functional Homologies of Ras Proteins............................................................121
D. Regulation of Ras Protein Activity............................................................................................122
E. Functional Activities of Ras Proteins........................................................................................124
F. Mutant c-Ras Proteins.................................................................................................................125
G. Role of Ras Proteins in Cell Proliferation and Differentiation................................................126
H. Ras Proteins and the Mechanisms of Growth Factor Action..................................................128
I. Other Functions of Ras Proteins................................................................................................130
J. Role of Growth Factors in ras-Induced Transformation.........................................................131
References......................................................................................................................................................131
Chapter 6
The Calcium-Calmodulin System
I. Introduction.........................................................................................................................................147
II. Calcium Ions.....................................................................................................................................148
III. Calmodulin.........................................................................................................................................150
A. Calmodulin Genes.......................................................................................................................150
B. Structure and Function of Calmodulin......................................................................................150
C. Regulation of Calmodulin Activity............................................................................................151
IV. The Calcium/Calmodulin System in the Control of Cell Proliferation
and Differentiation.............................................................................................................................151
A. Regulation of Proto-Oncogene Expression by Calcium.........................................................152
B. The Calcium/Calmodulin System in Malignant Transformation.............................................153
C. Requirement of Neoplastic Cells for Extracellular Calcium..................................................154
D. Role of Calcium in Neoplastic Cell Differentiation...............................................................154
E. Presence of Calmodulin in Retroviruses....................................................................................155
V. Calcium/Calmodulin-Dependent Protein Kinases............................................................................155
VI. Other Calcium-Binding Proteins.......................................................................................................156
References......................................................................................................................................................158
Chapter 7
Phosphoinositide Metabolism
I. Introduction.........................................................................................................................................169
II. Phosphatidylinositol Metabolism....................................................................................................169
A. Phospholipase C ...........................................................................................................................169
B. Products of Phosphatidylinositol Hydrolysis............................................................................171
C. Phospholipase D ...........................................................................................................................172
D. Phospholipase A2..........................................................................................................................173
E. Phosphatidylinositol Kinases.......................................................................................................173
F. Cyclic Esters of Inositol Phosphates..........................................................................................174
G. Platelet-Activating Factor............................................................................................................174
III. Protein Kinase C ................................................................................................................................175
A. Structure of Protein Kinase C and the Protein Kinase C Gene............................................175
B. Protein Kinase C Isoenzymes....................................................................................................176
C. Subcellular Localization of Protein Kinase C ..........................................................................177
D. Regulation and Function of Protein Kinase C..........................................................................177
E. Protein Kinase C Inhibitors.........................................................................................................178
F. Phosphorylation and Downregulation of Protein Kinase C .....................................................178
G. Protein Kinase P...........................................................................................................................179
H. Mutant Protein Kinase C.............................................................................................................179
IV. Phosphoinositide Metabolism and Cell Proliferation.....................................................................179
A. Activation of DNA Polymerase.................................................................................................179
B. Influence of Calcium Ions...........................................................................................................180
C. Changes in Ion Fluxes and Distribution....................................................................................180
D. Release and Activation of Ornithine Decarboxylase................................................................181
E. Cellular Substrates for Protein Kinase C...................................................................................181
F. Regulation of Receptors for Endogenous Mediators..............................................................181
G. Regulation of Cell Proliferation and Differentiation..............................................................182
H. Regulation of Phosphoinositide Turnover by Growth Factors..............................................182
V. Phosphoinositide Metabolism and Neoplasia.................................................................................183
VI. Oncoproteins and Phosphoinositide Metabolism............................................................................184
A. The src Gene Family...................................................................................................................184
B. The c-myc Gene............................................................................................................................186
C. The c-fos and c-jun Genes........................................................................................................186
D. The ras Genes...............................................................................................................................187
VII. Sphingolipid Metabolism..................................................................................................................187
References......................................................................................................................................................188
Chapter 8
Protein Phosphorylation
I. Introduction.........................................................................................................................................207
II. Tyrosine-Specific Protein Kinase Activity.....................................................................................208
A. Tyrosine Kinase Oncoproteins...................................................................................................210
1. The Src Protein......................................................................................................................210
2. The Abl Protein......................................................................................................................213
3. The Ros Protein......................................................................................................................214
4. The Fes/Fps Protein................................................................................................................215
5. The Fgr Protein......................................................................................................................215
6. The Yes Protein......................................................................................................................216
7. The Sea Protein......................................................................................................................216
8. The Ryk Protein.....................................................................................................................217
B. Other Putative Tyrosine Kinase Oncoproteins........................................................................217
1. The Fyn/Syn/Slk Protein.......................................................................................................217
2. The Lck/Lsk/Tck Protein......................................................................................................218
3. The Blk Protein......................................................................................................................219
4. The Hck/Bmk Protein...........................................................................................................219
5. The Lyn Protein......................................................................................................................219
6. The Arg Protein......................................................................................................................220
7. The Eph Protein......................................................................................................................220
8. The Ret Protein ......................................................................................................................220
9. The Fer/Flk Protein................................................................................................................220
10. The Tec Protein......................................................................................................................221
11. The Ltk Protein .....................................................................................................................221
12. The Nyk Protein.....................................................................................................................221
13. The Hyk Protein.....................................................................................................................221
14. The Syk Protein......................................................................................................................221
15. The Axl Protein......................................................................................................................222
16. The Tie Protein.......................................................................................................................222
17. The Ror Proteins ....................................................................................................................222
18. The Tek Protein......................................................................................................................222
C. Tyrosine Phosphorylation and the Mechanism of Action of Growth Factors.....................222
D. Substrates of Tyrosine-Specific Protein Kinases.....................................................................223
E. Tyrosine Kinases in Normal Cells.............................................................................................225
F. Tyrosine Kinases in Malignant Cells........................................................................................225
III. Phosphotyrosine-Specific Protein Phosphatases.............................................................................226
A. Subcellular Localization and Function of Protein-Tyrosine Phosphatases..........................227
B. Molecular Forms of Protein-Tyrosine Phosphatases...............................................................227
C. Regulation of Protein-Tyrosine Phosphatase Activity.............................................................229
D. Role of Protein-Tyrosine Phosphatases in Transformation......................................................229
IV. Serine/Threonine-Specific Protein Kinases....................................................................................230
A. The Mos Protein..........................................................................................................................232
B. The Raf/Mil Proteins...................................................................................................................233
C. The Pim-1 Protein.......................................................................................................................235
D. The Akt/Rac Protein....................................................................................................................235
E. The Cot Proteins...........................................................................................................................235
F. Substrates for Serine/Threonine-Specific Protein Kinases.....................................................235
G. Serine/Threonine Kinases and Neoplastic Transformation....................................................236
V. Serine/Threonine-Specific Protein Phosphatases.........................................................................236
References......................................................................................................................................................237
Chapter 9
Proto-Oncogene and Onco-Suppressor Gene Expression
I. Introduction.........................................................................................................................................267
II. Expression and Function of Nuclear Oncoproteins........................................................................269
A. The Myc Protein Family.............................................................................................................271
B. The Myb Protein Family.............................................................................................................274
C. The Fos Protein Family...............................................................................................................275
D. The Jun Protein Family...............................................................................................................277
E. The Ets Protein Family...............................................................................................................279
F. The Rel Protein Family...............................................................................................................280
G. The Egr/Krox Proteins.................................................................................................................281
H. The Vav Protein...........................................................................................................................282
III. Expression and Function of Tumor Suppressor Proteins.............................................................282
A. The p53 Gene..............................................................................................................................282
B. TheR57 Gene.............................................................................................................................284
C. The WT1 Gene..............................................................................................................................286
D. The NF1 Gene..............................................................................................................................287
E. The BTG1 Gene............................................................................................................................287
IV. Regulation of Oncoprotein and Tumor Suppressor Protein Expression
by Extracellular Agents...................................................................................................................287
A. Mitogenic Agents........................................................................................................................287
B. Tissue Regeneration and Compensatory Cell Growth............................................................288
C. Dietary Influences.......................................................................................................................290
D. Growth Factors............................................................................................................................290
V. Mechanisms of Proto-Oncogene Regulation by Growth Factors...............................................291
A. Mechanisms of Regulation of c-myc Gene Expression...........................................................292
B. Mechanisms of Regulation of c-fos Gene Expression............................................................293
C. Intracellular Mediators Involved in the Regulation of c-fos and c-myc
Gene Expression..........................................................................................................................294
VI. Physiological Significance of Growth Factor-Regulated Proto-Oncogene Expression..............295
A. Nuclear Oncoproteins and Cellular Proliferation....................................................................295
B. Nuclear Oncoproteins and Cellular Differentiation.................................................................297
C. Unspecific Stimulation of Proto-Oncogene Expression..........................................................299
References......................................................................................................................................................300
Chapter 10
Role of Growth Factors in Neoplastic Processes
I. Introduction.......................................................................................................................................329
II. Growth Factors and Oncogenesis....................................................................................................329
A. Growth Factor-Induced Neoplastic Transformation................................................................330
B. Influence of the Transforming Agent.......................................................................................330
C. Influence of the Type of Cell....................................................................................................331
D. Requirement for Multiple Hormones and Growth Factors.....................................................332
E. Angiogenic Factors and Stromal Factors..................................................................................332
III. Autocrine Mechanisms in Oncogenesis...........................................................................................333
IV. Growth Factors and Viral Oncoproteins..........................................................................................336
References......................................................................................................................................................337
Index 347